rs1714746

Variant names:

• chr8-4247625-G-A
• rs1714746
• NM_033225.6:c.415+172328C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-4247625-G-A
• chr8-4247625-G-C
• chr8-4247625-G-T

Variant summary

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

The NM_033225.6(CSMD1):​c.415+172328C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,886 control chromosomes in the GnomAD database, including 23,330 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 0.54 (23330 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.415+172328C>T		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.415+172328C>T		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.415+172328C>T		intron_variant	Intron 3 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.415+172328C>T		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82444 AN: 151768 Hom.: 23330 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.543 AC: 82456 AN: 151886 Hom.: 23330 Cov.: 33 AF XY: 0.543 AC XY: 40285 AN XY: 74194

African (AFR) AF: 0.358 AC: 14810 AN: 41410

American (AMR) AF: 0.550 AC: 8380 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2259 AN: 3470

East Asian (EAS) AF: 0.475 AC: 2446 AN: 5150

South Asian (SAS) AF: 0.588 AC: 2835 AN: 4824

European-Finnish (FIN) AF: 0.628 AC: 6599 AN: 10506

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43246 AN: 67972

Other (OTH) AF: 0.557 AC: 1176 AN: 2112

Alfa AF: 0.597 Hom.: 78460

Bravo AF: 0.527

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.47
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1714746; hg19: chr8-4105147;