NM_033225.6:c.416-8708A>C

Variant names:

• chr8-4040807-T-G
• rs2912272
• NM_033225.6:c.416-8708A>C

Variant summary

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

The NM_033225.6(CSMD1):​c.416-8708A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,236 control chromosomes in the GnomAD database, including 67,761 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 0.94 (67761 hom., cov: 31)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.416-8708A>C		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.416-8708A>C		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.416-8708A>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.416-8708A>C		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143418 AN: 152118 Hom.: 67699 Cov.: 31

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.953

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.944

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

GnomAD4 genome AF: 0.943 AC: 143538 AN: 152236 Hom.: 67761 Cov.: 31 AF XY: 0.946 AC XY: 70378 AN XY: 74420

African (AFR) AF: 0.983 AC: 40831 AN: 41542

American (AMR) AF: 0.956 AC: 14616 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.953 AC: 3308 AN: 3472

East Asian (EAS) AF: 0.989 AC: 5107 AN: 5164

South Asian (SAS) AF: 0.958 AC: 4623 AN: 4828

European-Finnish (FIN) AF: 0.935 AC: 9909 AN: 10596

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61996 AN: 68026

Other (OTH) AF: 0.945 AC: 1994 AN: 2110

Alfa AF: 0.921 Hom.: 76772

Bravo AF: 0.944

Asia WGS AF: 0.969 AC: 3371 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	0.94
DANN	Benign	0.70
PhyloP100		-1.1
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: rs2912272; hg19: chr8-3898329;