8-4543602-A-G

Position:

• chr8-4543602-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.302+93740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 149,426 control chromosomes in the GnomAD database, including 6,793 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 0.29 (6793 hom., cov: 26)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.302+93740T>C		intron_variant		ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.302+93740T>C		intron_variant			XP_011533054.1
CSMD1	XM_017013731.2	c.302+93740T>C		intron_variant			XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.302+93740T>C		intron_variant		5	NM_033225.6	ENSP00000489225	P4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 42642 AN: 149312 Hom.: 6791 Cov.: 26

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.285 AC: 42644 AN: 149426 Hom.: 6793 Cov.: 26 AF XY: 0.286 AC XY: 20793 AN XY: 72708

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.310

Alfa AF: 0.339 Hom.: 18463

Bravo AF: 0.277

Asia WGS AF: 0.351 AC: 1220 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	0.090
DANN	Benign	0.44

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: rs11786902; hg19: chr8-4401124;