Variant chr4-118723660-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_014822.4(SEC24D):c.2959-6_2959-5insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,248,412 control chromosomes in the GnomAD database, including 585 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 93 hom., cov: 32)

Exomes 𝑓: 0.066 ( 492 hom. )

Consequence

SEC24D
NM_014822.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.471

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 4-118723660-G-GA is Benign according to our data. Variant chr4-118723660-G-GA is described in ClinVar as [Benign]. Clinvar id is 1283265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC24D	NM_014822.4 linkuse as main transcript	c.2959-6_2959-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000280551.11
SEC24D	NM_001318066.2 linkuse as main transcript	c.2962-6_2962-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SEC24D	ENST00000280551.11 linkuse as main transcript	c.2959-6_2959-5insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_014822.4	P1	O94855-1
SEC24D	ENST00000511481.5 linkuse as main transcript	c.1852-6_1852-5insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1
SEC24D	ENST00000502830.1 linkuse as main transcript	n.288-6_288-5insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
SEC24D	ENST00000505134.5 linkuse as main transcript	n.3090-6_3090-5insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

4744

AN:

144400

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.0937

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.000595

Gnomad SAS

AF:

0.0399

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.110

Gnomad NFE

AF:

0.0387

Gnomad OTH

AF:

0.0479

GnomAD3 exomes

AF:

0.0736

AC:

10275

AN:

139688

Hom.:

AF XY:

0.0747

AC XY:

5672

AN XY:

75930

show subpopulations

Gnomad AFR exome

AF:

0.0476

Gnomad AMR exome

AF:

0.0793

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.0303

Gnomad SAS exome

AF:

0.0977

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.0732

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0658

AC:

72648

AN:

1103942

Hom.:

492

Cov.:

AF XY:

0.0666

AC XY:

36409

AN XY:

546546

show subpopulations

Gnomad4 AFR exome

AF:

0.0495

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.0791

Gnomad4 FIN exome

AF:

0.0451

Gnomad4 NFE exome

AF:

0.0660

Gnomad4 OTH exome

AF:

0.0726

GnomAD4 genome

AF:

0.0328

AC:

4743

AN:

144470

Hom.:

Cov.:

AF XY:

0.0318

AC XY:

2237

AN XY:

70250

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.0309

Gnomad4 ASJ

AF:

0.0878

Gnomad4 EAS

AF:

0.000597

Gnomad4 SAS

AF:

0.0398

Gnomad4 FIN

AF:

0.0197

Gnomad4 NFE

AF:

0.0387

Gnomad4 OTH

AF:

0.0475

Bravo

AF:

0.0309

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 18, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Cole-Carpenter syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over