8-3066447-A-G

Position:

• chr8-3066447-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.7475-13800T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,046 control chromosomes in the GnomAD database, including 17,753 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 0.48 (17753 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.7475-13800T>C		intron_variant		ENST00000635120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.7475-13800T>C		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72491 AN: 151928 Hom.: 17751 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.477 AC: 72513 AN: 152046 Hom.: 17753 Cov.: 32 AF XY: 0.480 AC XY: 35674 AN XY: 74314

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.442

Alfa AF: 0.506 Hom.: 21461

Bravo AF: 0.465

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.50

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: rs7013027; hg19: chr8-2923969;