rs6822035

Positions:

• chr4-118789266-A-C
• chr4-118789266-A-T

Variant summary

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

The NM_014822.4(SEC24D):​c.1041+8417T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,116 control chromosomes in the GnomAD database, including 30,749 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 0.61 (30749 hom., cov: 32)
• Consequence: SEC24D NM_014822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC24D	NM_014822.4	c.1041+8417T>G		intron_variant		ENST00000280551.11	NP_055637.2
SEC24D	NM_001318066.2	c.1044+8417T>G		intron_variant			NP_001304995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC24D	ENST00000280551.11	c.1041+8417T>G		intron_variant		1	NM_014822.4	ENSP00000280551.6
SEC24D	ENST00000509818.5	n.*256+8417T>G		intron_variant		1		ENSP00000424085.1
SEC24D	ENST00000514561.5	n.*1015+8417T>G		intron_variant		1		ENSP00000422717.1
SEC24D	ENST00000419654.6	c.-292+8417T>G		intron_variant		5		ENSP00000388324.2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92958 AN: 151998 Hom.: 30725 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.612 AC: 93023 AN: 152116 Hom.: 30749 Cov.: 32 AF XY: 0.619 AC XY: 46004 AN XY: 74342

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.597

Alfa AF: 0.691 Hom.: 17639

Bravo AF: 0.589

Asia WGS AF: 0.645 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.87
DANN	Benign	0.41

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: rs6822035; hg19: chr4-119710421;