rs7005969

Positions:

• chr8-3081174-G-A
• chr8-3081174-G-C

Variant summary

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

The NM_033225.6(CSMD1):​c.7474+5923C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,174 control chromosomes in the GnomAD database, including 1,839 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 0.15 (1839 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.7474+5923C>T		intron_variant		ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.7474+5923C>T		intron_variant		5	NM_033225.6	ENSP00000489225	P4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23151 AN: 152056 Hom.: 1837 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.152 AC: 23174 AN: 152174 Hom.: 1839 Cov.: 33 AF XY: 0.149 AC XY: 11082 AN XY: 74414

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0833

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.146

Alfa AF: 0.145 Hom.: 953

Bravo AF: 0.151

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.085
DANN	Benign	0.55

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: rs7005969; hg19: chr8-2938696; COSMIC: COSV59341715;