rs77378271

Positions:

• chr8-3215967-A-G

Variant summary

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

The NM_033225.6(CSMD1):​c.4673-1276T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 150,340 control chromosomes in the GnomAD database, including 345 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 0.060 (345 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.4673-1276T>C		intron_variant		ENST00000635120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.4673-1276T>C		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 8949 AN: 150302 Hom.: 343 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0584

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0639

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

GnomAD4 genome AF: 0.0596 AC: 8954 AN: 150340 Hom.: 345 Cov.: 33 AF XY: 0.0602 AC XY: 4420 AN XY: 73374

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0579

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0542 Hom.: 30

Bravo AF: 0.0593

Asia WGS AF: 0.123 AC: 422 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.29
DANN	Benign	0.38

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: rs77378271; hg19: chr8-3073489;