8-4825228-T-G

Variant names:

• chr8-4825228-T-G
• rs11774281
• NM_033225.6:c.85+169104A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.85+169104A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,960 control chromosomes in the GnomAD database, including 5,180 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 0.25 (5180 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 1 publications found

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]

PAICSP4 (HGNC:38097): (phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase pseudogene 4)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.85+169104A>C		intron_variant	Intron 1 of 69	ENST00000635120.2	NP_150094.5
PAICSP4		n.4825228T>G		intragenic_variant
CSMD1	XM_011534752.3	c.85+169104A>C		intron_variant	Intron 1 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.85+169104A>C		intron_variant	Intron 1 of 63		XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.85+169104A>C		intron_variant	Intron 1 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38394 AN: 151842 Hom.: 5174 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.253 AC: 38416 AN: 151960 Hom.: 5180 Cov.: 32 AF XY: 0.253 AC XY: 18788 AN XY: 74268

African (AFR) AF: 0.161 AC: 6680 AN: 41486

American (AMR) AF: 0.284 AC: 4328 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1025 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1982 AN: 5156

South Asian (SAS) AF: 0.294 AC: 1420 AN: 4828

European-Finnish (FIN) AF: 0.297 AC: 3131 AN: 10538

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18920 AN: 67934

Other (OTH) AF: 0.253 AC: 534 AN: 2108

Alfa AF: 0.267 Hom.: 9188

Bravo AF: 0.249

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.43
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11774281; hg19: chr8-4682750;