4-118723660-GAAAA-GAAA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS1

The NM_014822.4(SEC24D):c.2959-6delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,430,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SEC24D
NM_014822.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.471

Publications

1 publications found

Variant links:

Genes affected

SEC24D (HGNC:10706): (SEC24 homolog D, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. This gene product is implicated in the shaping of the vesicle, and also in cargo selection and concentration. Mutations in this gene have been associated with Cole-Carpenter syndrome, a disorder affecting bone formation, resulting in craniofacial malformations and bones that break easily. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC24D Gene-Disease associations (from GenCC):

Cole-Carpenter syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
Cole-Carpenter syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
osteogenesis imperfecta type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SEC24D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 4-118723660-GA-G is Benign according to our data. Variant chr4-118723660-GA-G is described in ClinVar as Benign. ClinVar VariationId is 2052472.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000899 (13/144588) while in subpopulation EAS AF = 0.00179 (9/5026). AF 95% confidence interval is 0.000934. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014822.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24D	NM_014822.4	MANE Select	c.2959-6delT		splice_region intron	N/A	NP_055637.2	O94855-1
	SEC24D	NM_001318066.2		c.2962-6delT		splice_region intron	N/A	NP_001304995.1	O94855-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEC24D	ENST00000280551.11	TSL:1 MANE Select	c.2959-6delT	splice_region intron	N/A	ENSP00000280551.6	O94855-1
SEC24D	ENST00000511481.5	TSL:1	c.1852-6delT	splice_region intron	N/A	ENSP00000425491.1	E9PDM8
SEC24D	ENST00000924655.1		c.2959-6delT	splice_region intron	N/A	ENSP00000594714.1

Frequencies

GnomAD3 genomes

AF:

0.0000900

AC:

AN:

144518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00179

Gnomad SAS

AF:

0.000222

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00145

AC:

203

AN:

139688

AF XY:

0.00145

show subpopulations

Gnomad AFR exome

AF:

0.000977

Gnomad AMR exome

AF:

0.000628

Gnomad ASJ exome

AF:

0.00262

Gnomad EAS exome

AF:

0.00264

Gnomad FIN exome

AF:

0.000451

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000119

AC:

153

AN:

1286232

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

638146

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000719

AC:

AN:

27824

American (AMR)

AF:

0.000362

AC:

AN:

33190

Ashkenazi Jewish (ASJ)

AF:

0.0000449

AC:

AN:

22248

East Asian (EAS)

AF:

0.000945

AC:

AN:

33874

South Asian (SAS)

AF:

0.000298

AC:

AN:

70362

European-Finnish (FIN)

AF:

0.000129

AC:

AN:

46546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5218

European-Non Finnish (NFE)

AF:

0.0000754

AC:

AN:

994376

Other (OTH)

AF:

0.0000761

AC:

AN:

52594

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.369

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000899

AC:

AN:

144588

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

70316

show subpopulations

African (AFR)

AF:

0.0000507

AC:

AN:

39478

American (AMR)

AF:

0.00

AC:

AN:

14462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00179

AC:

AN:

5026

South Asian (SAS)

AF:

0.000222

AC:

AN:

4504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

65542

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000106

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over