rs142816172

Positions:

• chr8-3298698-C-T

Variant summary

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

The NM_033225.6(CSMD1):​c.3950+8997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 152,312 control chromosomes in the GnomAD database, including 41 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 0.020 (41 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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=-1.02).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0197 (2993/152312) while in subpopulation EAS AF= 0.0318 (165/5182). AF 95% confidence interval is 0.0279. There are 41 homozygotes in gnomad4. There are 1408 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.3950+8997G>A		intron_variant		ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.3950+8997G>A		intron_variant			XP_011533054.1
CSMD1	XM_011534753.4	c.1043+8997G>A		intron_variant			XP_011533055.1
CSMD1	XM_017013731.2	c.3950+8997G>A		intron_variant			XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.3950+8997G>A		intron_variant		5	NM_033225.6	ENSP00000489225	P4

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2992 AN: 152196 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.00543

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0210

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

GnomAD4 genome AF: 0.0197 AC: 2993 AN: 152312 Hom.: 41 Cov.: 33 AF XY: 0.0189 AC XY: 1408 AN XY: 74468

Gnomad4 AFR AF: 0.00541

Gnomad4 AMR AF: 0.0182

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.0269

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0227 Hom.: 4

Bravo AF: 0.0189

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.56

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: rs142816172; hg19: chr8-3156220;