8-112735587-C-T

Position:

• chr8-112735587-C-T

Variant summary

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

The NM_198123.2(CSMD3):​c.1973-45537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,792 control chromosomes in the GnomAD database, including 9,272 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 0.33 (9272 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

CSMD3 (HGNC:19291): (CUB and Sushi multiple domains 3) Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.1973-45537G>A		intron_variant		ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.1973-45537G>A		intron_variant		1	NM_198123.2	ENSP00000297405	P1
CSMD3	ENST00000343508.7	c.1853-45537G>A		intron_variant		1		ENSP00000345799
CSMD3	ENST00000455883.2	c.1661-45537G>A		intron_variant		1		ENSP00000412263

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50475 AN: 151674 Hom.: 9265 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.333 AC: 50512 AN: 151792 Hom.: 9272 Cov.: 32 AF XY: 0.336 AC XY: 24917 AN XY: 74170

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.298

Alfa AF: 0.300 Hom.: 1219

Bravo AF: 0.339

Asia WGS AF: 0.318 AC: 1104 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	0.17
DANN	Benign	0.39

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: rs1019603; hg19: chr8-113747816;