8-112643523-T-C

Variant names:

• chr8-112643523-T-C
• rs10505168
• NM_198123.2:c.3310+1586A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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:37069): (microRNA 2053) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.3310+1586A>G		intron_variant	Intron 20 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.3310+1586A>G		intron_variant	Intron 20 of 70	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

GnomAD2 exomes AF: 0.330 AC: 7757 AN: 23476 AF XY: 0.322

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 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

African (AFR) AF: 0.446 AC: 33 AN: 74

American (AMR) AF: 0.167 AC: 2 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.289 AC: 26 AN: 90

European-Finnish (FIN) AF: 0.358 AC: 5635 AN: 15742

Middle Eastern (MID) AF: 0.250 AC: 377 AN: 1510

European-Non Finnish (NFE) AF: 0.308 AC: 80 AN: 260

Other (OTH) AF: 0.353 AC: 98 AN: 278

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

African (AFR) AF: 0.499 AC: 20698 AN: 41444

American (AMR) AF: 0.316 AC: 4827 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3462

East Asian (EAS) AF: 0.420 AC: 2168 AN: 5166

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4812

European-Finnish (FIN) AF: 0.344 AC: 3637 AN: 10568

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18917 AN: 67902

Other (OTH) AF: 0.315 AC: 665 AN: 2114

Alfa AF: 0.315 Hom.: 12687

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
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10505168; hg19: chr8-113655752; COSMIC: COSV52166930;