8-4086560-G-C

Variant names:

• chr8-4086560-G-C
• rs10503232
• NM_033225.6:c.416-54461C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.416-54461C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,200 control chromosomes in the GnomAD database, including 970 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 0.11 (970 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.416-54461C>G		intron_variant	Intron 3 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.416-54461C>G		intron_variant	Intron 3 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.416-54461C>G		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.416-54461C>G		intron_variant	Intron 3 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16328 AN: 152082 Hom.: 973 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.107 AC: 16337 AN: 152200 Hom.: 970 Cov.: 33 AF XY: 0.106 AC XY: 7891 AN XY: 74396

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0238

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0943

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0437 Hom.: 40

Bravo AF: 0.107

Asia WGS AF: 0.0880 AC: 307 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	3.7
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503232; hg19: chr8-3944082;