chr8-3196070-G-A

Position:

• chr8-3196070-G-A

Variant summary

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

The NM_033225.6(CSMD1):​c.5194+3644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 152,194 control chromosomes in the GnomAD database, including 184 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 0.048 (184 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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 = 0.0821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.5194+3644C>T		intron_variant		ENST00000635120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.5194+3644C>T		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7244 AN: 152076 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0477 AC: 7259 AN: 152194 Hom.: 184 Cov.: 32 AF XY: 0.0484 AC XY: 3598 AN XY: 74410

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.0674

Gnomad4 SAS AF: 0.0891

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0455

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0429 Hom.: 141

Bravo AF: 0.0480

Asia WGS AF: 0.0840 AC: 291 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	6.0
DANN	Benign	0.56

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: rs1077153; hg19: chr8-3053592; COSMIC: COSV59334360;