8-3408068-C-T

Position:

• chr8-3408068-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_033225.6(CSMD1):​c.1902G>A​(p.Gln634Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,613,398 control chromosomes in the GnomAD database, including 347,504 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 0.66 (33224 hom., cov: 30)
  • Exomes 𝑓: 0.65 (314280 hom.)
• Consequence: CSMD1 NM_033225.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.423 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.1902G>A	p.Gln634Gln	synonymous_variant	14/70	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.1902G>A	p.Gln634Gln	synonymous_variant	14/69		XP_011533054.1
CSMD1	XM_017013731.2	c.1902G>A	p.Gln634Gln	synonymous_variant	14/64		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.1902G>A	p.Gln634Gln	synonymous_variant	14/70	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99845 AN: 151724 Hom.: 33204 Cov.: 30

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.698

GnomAD3 exomes AF: 0.629 AC: 156658 AN: 248940 Hom.: 50390 AF XY: 0.636 AC XY: 85934 AN XY: 135034

Gnomad AFR exome AF: 0.688

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.371

Gnomad SAS exome AF: 0.655

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.666

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.653 AC: 954941 AN: 1461556 Hom.: 314280 Cov.: 61 AF XY: 0.654 AC XY: 475679 AN XY: 727062

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.582

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.652

GnomAD4 genome AF: 0.658 AC: 99913 AN: 151842 Hom.: 33224 Cov.: 30 AF XY: 0.655 AC XY: 48584 AN XY: 74176

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.696

Alfa AF: 0.662 Hom.: 66212

Bravo AF: 0.657

Asia WGS AF: 0.517 AC: 1797 AN: 3478

EpiCase AF: 0.673

EpiControl AF: 0.685

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.0
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10088378; hg19: chr8-3265590; COSMIC: COSV59298320;