chr8-2954749-C-A

Variant names:

• chr8-2954749-C-A
• rs865303
• NM_033225.6:c.9995-481G>T

Variant summary

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

The NM_033225.6(CSMD1):​c.9995-481G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,196 control chromosomes in the GnomAD database, including 46,900 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 0.78 (46900 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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]

LOC105377785 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.9995-481G>T		intron_variant	Intron 64 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.9995-481G>T		intron_variant	Intron 64 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119129 AN: 152078 Hom.: 46864 Cov.: 33

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.783 AC: 119214 AN: 152196 Hom.: 46900 Cov.: 33 AF XY: 0.786 AC XY: 58470 AN XY: 74414

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.749

Alfa AF: 0.777 Hom.: 55159

Bravo AF: 0.773

Asia WGS AF: 0.696 AC: 2420 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	0.25
DANN	Benign	0.39

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: rs865303; hg19: chr8-2812271;