8-3107722-T-C

Position:

• chr8-3107722-T-C

Variant summary

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

The NM_033225.6(CSMD1):​c.6831A>G​(p.Glu2277Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,571,648 control chromosomes in the GnomAD database, including 515,900 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 0.80 (48543 hom., cov: 32)
  • Exomes 𝑓: 0.81 (467357 hom.)
• Consequence: CSMD1 NM_033225.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.126 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.6831A>G	p.Glu2277Glu	synonymous_variant	45/70	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.6831A>G	p.Glu2277Glu	synonymous_variant	45/70	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121191 AN: 152020 Hom.: 48524 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.805

GnomAD3 exomes AF: 0.828 AC: 189612 AN: 228906 Hom.: 79031 AF XY: 0.829 AC XY: 103557 AN XY: 124988

Gnomad AFR exome AF: 0.735

Gnomad AMR exome AF: 0.892

Gnomad ASJ exome AF: 0.829

Gnomad EAS exome AF: 0.958

Gnomad SAS exome AF: 0.875

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.822

GnomAD4 exome AF: 0.810 AC: 1149663 AN: 1419510 Hom.: 467357 Cov.: 25 AF XY: 0.812 AC XY: 574889 AN XY: 707834

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.886

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.878

Gnomad4 FIN exome AF: 0.808

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.797 AC: 121263 AN: 152138 Hom.: 48543 Cov.: 32 AF XY: 0.801 AC XY: 59578 AN XY: 74378

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.805

Alfa AF: 0.800 Hom.: 78829

Bravo AF: 0.797

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.1
DANN	Benign	0.47

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: rs3824271; hg19: chr8-2965244;