rs10503238

Variant names:

• chr8-4182535-A-G
• rs10503238
• NM_033225.6:c.416-150436T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-4182535-A-G
• chr8-4182535-A-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.416-150436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,068 control chromosomes in the GnomAD database, including 8,651 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 0.30 (8651 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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 = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.416-150436T>C		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.416-150436T>C		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.416-150436T>C		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.416-150436T>C		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45468 AN: 151950 Hom.: 8648 Cov.: 32

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.299 AC: 45473 AN: 152068 Hom.: 8651 Cov.: 32 AF XY: 0.303 AC XY: 22513 AN XY: 74306

African (AFR) AF: 0.0753 AC: 3126 AN: 41512

American (AMR) AF: 0.347 AC: 5309 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3472

East Asian (EAS) AF: 0.0840 AC: 433 AN: 5156

South Asian (SAS) AF: 0.362 AC: 1745 AN: 4818

European-Finnish (FIN) AF: 0.462 AC: 4881 AN: 10558

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27522 AN: 67960

Other (OTH) AF: 0.312 AC: 658 AN: 2108

Alfa AF: 0.367 Hom.: 15831

Bravo AF: 0.280

Asia WGS AF: 0.255 AC: 886 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	0.099
DANN	Benign	0.25
PhyloP100		-1.4
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: rs10503238; hg19: chr8-4040057;