rs3802292

Positions:

• chr8-3108806-T-C
• chr8-3108806-T-G

Variant summary

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

The NM_033225.6(CSMD1):​c.6609-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,515,150 control chromosomes in the GnomAD database, including 215,815 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 0.52 (20398 hom., cov: 33)
  • Exomes 𝑓: 0.53 (195417 hom.)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.6609-58A>G		intron_variant		ENST00000635120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.6609-58A>G		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78298 AN: 151946 Hom.: 20388 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.534 AC: 728172 AN: 1363088 Hom.: 195417 AF XY: 0.536 AC XY: 360285 AN XY: 672400

Gnomad4 AFR exome AF: 0.433

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.515 AC: 78342 AN: 152062 Hom.: 20398 Cov.: 33 AF XY: 0.523 AC XY: 38826 AN XY: 74306

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.518

Alfa AF: 0.516 Hom.: 27277

Bravo AF: 0.510

Asia WGS AF: 0.521 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.39

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: rs3802292; hg19: chr8-2966328; COSMIC: COSV59342179; COSMIC: COSV59342179;