rs1971078

chr8-4080073-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.416-47974T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,446 control chromosomes in the GnomAD database, including 14,985 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 0.42 (14985 hom., cov: 29)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.27

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSMD1	NM_033225.6	c.416-47974T>C		intron_variant		ENST00000635120.2
CSMD1	XM_011534752.3	c.416-47974T>C		intron_variant
CSMD1	XM_017013731.2	c.416-47974T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSMD1	ENST00000635120.2	c.416-47974T>C		intron_variant		5	NM_033225.6	P4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64011 AN: 151330 Hom.: 14989 Cov.: 29

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.423 AC: 64007 AN: 151446 Hom.: 14985 Cov.: 29 AF XY: 0.429 AC XY: 31684 AN XY: 73902

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.392

Alfa AF: 0.489 Hom.: 28401

Bravo AF: 0.394

Asia WGS AF: 0.426 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.088
Dann	Benign	0.31

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: rs1971078; hg19: chr8-3937595;