rs10503222

chr8-3916226-C-A

Variant summary

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

The NM_033225.6(CSMD1):c.818+81677G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 152,142 control chromosomes in the GnomAD database, including 18 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 0.012 (18 hom., cov: 30)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1778/152142) while in subpopulation NFE AF= 0.0177 (1206/68002). AF 95% confidence interval is 0.0169. There are 18 homozygotes in gnomad4. There are 822 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.818+81677G>T		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.818+81677G>T		intron_variant
CSMD1	XM_017013731.2	c.818+81677G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.818+81677G>T		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1777 AN: 152024 Hom.: 18 Cov.: 30

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00990

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.00956

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

GnomAD4 genome AF: 0.0117 AC: 1778 AN: 152142 Hom.: 18 Cov.: 30 AF XY: 0.0111 AC XY: 822 AN XY: 74382

Gnomad4 AFR AF: 0.00477

Gnomad4 AMR AF: 0.00989

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.0135 Hom.: 1

Bravo AF: 0.0114

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.3
Dann	Benign	0.36

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: rs10503222; hg19: chr8-3773748;