rs246341

Positions:

• chr5-134698087-G-A
• chr5-134698087-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021982.3(SEC24A):​c.2266+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,572,916 control chromosomes in the GnomAD database, including 739,538 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 0.98 (72844 hom., cov: 29)
  • Exomes 𝑓: 0.97 (666694 hom.)
• Consequence: SEC24A NM_021982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403

Genes affected

SEC24A (HGNC:10703): (SEC24 homolog A, COPII coat complex component) The protein encoded by this gene belongs to a family of proteins that are homologous to yeast Sec24. This protein is a component of coat protein II (COPII)-coated vesicles that mediate protein transport from the endoplasmic reticulum. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC24A	NM_021982.3	c.2266+30G>A		intron_variant		ENST00000398844.7	NP_068817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC24A	ENST00000398844.7	c.2266+30G>A		intron_variant		2	NM_021982.3	ENSP00000381823.2

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148730 AN: 152030 Hom.: 72781 Cov.: 29

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.983

GnomAD3 exomes AF: 0.977 AC: 220095 AN: 225330 Hom.: 107518 AF XY: 0.976 AC XY: 119454 AN XY: 122420

Gnomad AFR exome AF: 0.994

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 0.974

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.980

Gnomad FIN exome AF: 0.975

Gnomad NFE exome AF: 0.967

Gnomad OTH exome AF: 0.978

GnomAD4 exome AF: 0.969 AC: 1376251 AN: 1420768 Hom.: 666694 Cov.: 23 AF XY: 0.969 AC XY: 685581 AN XY: 707524

Gnomad4 AFR exome AF: 0.995

Gnomad4 AMR exome AF: 0.990

Gnomad4 ASJ exome AF: 0.974

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.981

Gnomad4 FIN exome AF: 0.977

Gnomad4 NFE exome AF: 0.964

Gnomad4 OTH exome AF: 0.972

GnomAD4 genome AF: 0.978 AC: 148852 AN: 152148 Hom.: 72844 Cov.: 29 AF XY: 0.979 AC XY: 72803 AN XY: 74376

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.990

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.983

Alfa AF: 0.972 Hom.: 21264

Bravo AF: 0.980

Asia WGS AF: 0.991 AC: 3447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs246341; hg19: chr5-134033777;