8-3107162-C-T

Position:

• chr8-3107162-C-T

Variant summary

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

The NM_033225.6(CSMD1):​c.6836-521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 155,370 control chromosomes in the GnomAD database, including 64,688 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 0.91 (63271 hom., cov: 32)
  • Exomes 𝑓: 0.95 (1417 hom.)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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]

CSMD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.6836-521G>A		intron_variant		ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.6836-521G>A		intron_variant		5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.907 AC: 138002 AN: 152102 Hom.: 63240 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.921

GnomAD4 exome AF: 0.947 AC: 2983 AN: 3150 Hom.: 1417 Cov.: 0 AF XY: 0.943 AC XY: 1576 AN XY: 1672

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.948

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 0.976

Gnomad4 SAS exome AF: 0.900

Gnomad4 FIN exome AF: 0.988

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.903

GnomAD4 genome AF: 0.907 AC: 138082 AN: 152220 Hom.: 63271 Cov.: 32 AF XY: 0.911 AC XY: 67812 AN XY: 74420

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.920

Alfa AF: 0.952 Hom.: 8784

Bravo AF: 0.900

Asia WGS AF: 0.920 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.035
DANN	Benign	0.16

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: rs10503193; hg19: chr8-2964684;