chr4-118743073-T-C

Variant names:

• chr4-118743073-T-C
• rs4834700
• NM_014822.4:c.1995+915A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014822.4(SEC24D):​c.1995+915A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,026 control chromosomes in the GnomAD database, including 45,493 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45493 hom., cov: 31)
• Consequence: SEC24D NM_014822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 2 publications found

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: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24D	NM_014822.4	MANE Select	c.1995+915A>G		intron	N/A	NP_055637.2
	SEC24D	NM_001318066.2		c.1998+915A>G		intron	N/A	NP_001304995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24D	ENST00000280551.11	TSL:1 MANE Select	c.1995+915A>G		intron	N/A	ENSP00000280551.6
	SEC24D	ENST00000511481.5	TSL:1	c.888+915A>G		intron	N/A	ENSP00000425491.1
	SEC24D	ENST00000514561.5	TSL:1	n.*2402+915A>G		intron	N/A	ENSP00000422717.1

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116700 AN: 151910 Hom.: 45449 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.815

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.768 AC: 116797 AN: 152026 Hom.: 45493 Cov.: 31 AF XY: 0.767 AC XY: 56970 AN XY: 74300

African (AFR) AF: 0.878 AC: 36406 AN: 41472

American (AMR) AF: 0.804 AC: 12280 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2975 AN: 3472

East Asian (EAS) AF: 0.815 AC: 4209 AN: 5164

South Asian (SAS) AF: 0.777 AC: 3735 AN: 4810

European-Finnish (FIN) AF: 0.627 AC: 6616 AN: 10556

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47944 AN: 67962

Other (OTH) AF: 0.813 AC: 1717 AN: 2112

Alfa AF: 0.735 Hom.: 66452

Bravo AF: 0.788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.32
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4834700; hg19: chr4-119664228;