rs1077153

Variant names:

• chr8-3196070-G-A
• rs1077153
• NM_033225.6:c.5194+3644C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-3196070-G-A
• chr8-3196070-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.5194+3644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 152,194 control chromosomes in the GnomAD database, including 184 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 0.048 (184 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 1 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 = 0.0821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	NM_033225.6	MANE Select	c.5194+3644C>T		intron	N/A	NP_150094.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.5194+3644C>T		intron	N/A	ENSP00000489225.1
	CSMD1	ENST00000335551.11	TSL:1	c.3634+3644C>T		intron	N/A	ENSP00000334828.6
	CSMD1	ENST00000523488.5	TSL:1	n.2727+3644C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7244 AN: 152076 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0477 AC: 7259 AN: 152194 Hom.: 184 Cov.: 32 AF XY: 0.0484 AC XY: 3598 AN XY: 74410

African (AFR) AF: 0.0401 AC: 1665 AN: 41534

American (AMR) AF: 0.0471 AC: 721 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 263 AN: 3470

East Asian (EAS) AF: 0.0674 AC: 348 AN: 5164

South Asian (SAS) AF: 0.0891 AC: 428 AN: 4806

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0455 AC: 3094 AN: 68000

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0440 Hom.: 205

Bravo AF: 0.0480

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.56
PhyloP100		0.36
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: rs1077153; hg19: chr8-3053592; COSMIC: COSV59334360;