rs1714757

Positions:

• chr8-4171991-A-C
• chr8-4171991-A-G

Variant summary

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

The NM_033225.6(CSMD1):​c.416-139892T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,020 control chromosomes in the GnomAD database, including 21,562 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 0.50 (21562 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.416-139892T>G		intron_variant		ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.416-139892T>G		intron_variant			XP_011533054.1
CSMD1	XM_017013731.2	c.416-139892T>G		intron_variant			XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.416-139892T>G		intron_variant		5	NM_033225.6	ENSP00000489225	P4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75477 AN: 151902 Hom.: 21559 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.497 AC: 75502 AN: 152020 Hom.: 21562 Cov.: 32 AF XY: 0.500 AC XY: 37111 AN XY: 74288

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.499

Alfa AF: 0.591 Hom.: 33758

Bravo AF: 0.476

Asia WGS AF: 0.447 AC: 1552 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.5
DANN	Benign	0.52

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: rs1714757; hg19: chr8-4029513;