rs10503191

chr8-3105974-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033225.6(CSMD1):c.6949+554C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 152,302 control chromosomes in the GnomAD database, including 33 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 0.017 (33 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

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).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0171 (2608/152302) while in subpopulation EAS AF= 0.0432 (224/5184). AF 95% confidence interval is 0.0386. There are 33 homozygotes in gnomad4. There are 1249 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.6949+554C>G		intron_variant		ENST00000635120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.6949+554C>G		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2608 AN: 152184 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.00466

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0171 AC: 2608 AN: 152302 Hom.: 33 Cov.: 32 AF XY: 0.0168 AC XY: 1249 AN XY: 74472

Gnomad4 AFR AF: 0.00464

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.0432

Gnomad4 SAS AF: 0.0246

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0177 Hom.: 3

Bravo AF: 0.0162

Asia WGS AF: 0.0460 AC: 160 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	1.3
Dann	Benign	0.57

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: rs10503191; hg19: chr8-2963496;