8-112473416-C-T

Variant names:

• chr8-112473416-C-T
• rs10505174
• NM_198123.2:c.5279-709G>A

Variant summary

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

The NM_198123.2(CSMD3):​c.5279-709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,812 control chromosomes in the GnomAD database, including 5,095 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 0.26 (5095 hom., cov: 32)
• Consequence: CSMD3 NM_198123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD3	NM_198123.2	c.5279-709G>A		intron_variant	Intron 31 of 70	ENST00000297405.10	NP_937756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD3	ENST00000297405.10	c.5279-709G>A		intron_variant	Intron 31 of 70	1	NM_198123.2	ENSP00000297405.5
CSMD3	ENST00000343508.7	c.5159-709G>A		intron_variant	Intron 32 of 71	1		ENSP00000345799.3
CSMD3	ENST00000455883.2	c.4967-709G>A		intron_variant	Intron 30 of 68	1		ENSP00000412263.2
CSMD3	ENST00000339701.7	c.3299-709G>A		intron_variant	Intron 18 of 55	1		ENSP00000341558.3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38757 AN: 151694 Hom.: 5091 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.255 AC: 38778 AN: 151812 Hom.: 5095 Cov.: 32 AF XY: 0.255 AC XY: 18925 AN XY: 74156

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.269

Alfa AF: 0.246 Hom.: 9842

Bravo AF: 0.270

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.070
DANN	Benign	0.70

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: rs10505174; hg19: chr8-113485645;