chr8-112643523-T-C

Position:

• chr8-112643523-T-C

Variant summary

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

The NM_198123.2(CSMD3):​c.3310+1586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 169,910 control chromosomes in the GnomAD database, including 11,265 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 0.35 (10179 hom., cov: 32)
  • Exomes 𝑓: 0.35 (1086 hom.)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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]

MIR2053 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.3310+1586A>G		intron_variant		ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.3310+1586A>G		intron_variant		1	NM_198123.2	ENSP00000297405.5

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53610 AN: 151818 Hom.: 10169 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.330 AC: 7757 AN: 23476 Hom.: 1334 AF XY: 0.322 AC XY: 3374 AN XY: 10476

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.269

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.348 AC: 6251 AN: 17974 Hom.: 1086 Cov.: 0 AF XY: 0.343 AC XY: 2954 AN XY: 8604

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.353 AC: 53662 AN: 151936 Hom.: 10179 Cov.: 32 AF XY: 0.357 AC XY: 26507 AN XY: 74274

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.315

Alfa AF: 0.325 Hom.: 985

Bravo AF: 0.360

Asia WGS AF: 0.369 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10505168; hg19: chr8-113655752; COSMIC: COSV52166930;