rs4834700

Positions:

• chr4-118743073-T-C
• chr4-118743073-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC24D	NM_014822.4	c.1995+915A>G		intron_variant		ENST00000280551.11
SEC24D	NM_001318066.2	c.1998+915A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC24D	ENST00000280551.11	c.1995+915A>G		intron_variant		1	NM_014822.4	P1

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

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.813

Alfa AF: 0.729 Hom.: 50918

Bravo AF: 0.788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.32

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

LitVar

Other links and lift over

dbSNP: rs4834700; hg19: chr4-119664228;