8-3108806-T-C

Variant names:

• chr8-3108806-T-C
• rs3802292
• NM_033225.6:c.6609-58A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.6609-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,515,150 control chromosomes in the GnomAD database, including 215,815 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 0.52 (20398 hom., cov: 33)
  • Exomes 𝑓: 0.53 (195417 hom.)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 7 publications found

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]

CSMD1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.6609-58A>G		intron_variant	Intron 43 of 69	ENST00000635120.2	NP_150094.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.6609-58A>G		intron_variant	Intron 43 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78298 AN: 151946 Hom.: 20388 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.534 AC: 728172 AN: 1363088 Hom.: 195417 AF XY: 0.536 AC XY: 360285 AN XY: 672400

African (AFR) AF: 0.433 AC: 12984 AN: 29960

American (AMR) AF: 0.623 AC: 18772 AN: 30154

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 10374 AN: 22860

East Asian (EAS) AF: 0.618 AC: 23564 AN: 38128

South Asian (SAS) AF: 0.598 AC: 45415 AN: 75920

European-Finnish (FIN) AF: 0.588 AC: 30030 AN: 51080

Middle Eastern (MID) AF: 0.541 AC: 2921 AN: 5402

European-Non Finnish (NFE) AF: 0.526 AC: 554261 AN: 1053336

Other (OTH) AF: 0.531 AC: 29851 AN: 56248

GnomAD4 genome AF: 0.515 AC: 78342 AN: 152062 Hom.: 20398 Cov.: 33 AF XY: 0.523 AC XY: 38826 AN XY: 74306

African (AFR) AF: 0.438 AC: 18168 AN: 41472

American (AMR) AF: 0.588 AC: 8991 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2958 AN: 5174

South Asian (SAS) AF: 0.608 AC: 2928 AN: 4812

European-Finnish (FIN) AF: 0.597 AC: 6298 AN: 10550

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35641 AN: 67984

Other (OTH) AF: 0.518 AC: 1094 AN: 2114

Alfa AF: 0.517 Hom.: 64828

Bravo AF: 0.510

Asia WGS AF: 0.521 AC: 1815 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	2.7
DANN	Benign	0.39
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3802292; hg19: chr8-2966328; COSMIC: COSV59342179; COSMIC: COSV59342179;