rs2265477

Variant names:

• chr6-145891202-T-C
• rs2265477
• NM_001042683.3:c.4874+2013A>G

Variant summary

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

The NM_001042683.3(SHPRH):​c.4874+2013A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,004 control chromosomes in the GnomAD database, including 17,499 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 0.47 (17499 hom., cov: 32)
• Consequence: SHPRH NM_001042683.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 11 publications found

Genes affected

SHPRH (HGNC:19336): (SNF2 histone linker PHD RING helicase) SHPRH is a ubiquitously expressed protein that contains motifs characteristics of several DNA repair proteins, transcription factors, and helicases. SHPRH is a functional homolog of S. cerevisiae RAD5 (Unk et al., 2006 [PubMed 17108083]).[supplied by OMIM, Mar 2008]

EPM2A-DT (HGNC:48990): (EPM2A divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHPRH	NM_001042683.3	c.4874+2013A>G		intron_variant	Intron 28 of 29	ENST00000275233.12	NP_001036148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHPRH	ENST00000275233.12	c.4874+2013A>G		intron_variant	Intron 28 of 29	1	NM_001042683.3	ENSP00000275233.7

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71924 AN: 151886 Hom.: 17477 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.474 AC: 71987 AN: 152004 Hom.: 17499 Cov.: 32 AF XY: 0.475 AC XY: 35294 AN XY: 74266

African (AFR) AF: 0.562 AC: 23278 AN: 41444

American (AMR) AF: 0.359 AC: 5481 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1587 AN: 3462

East Asian (EAS) AF: 0.353 AC: 1814 AN: 5144

South Asian (SAS) AF: 0.522 AC: 2519 AN: 4824

European-Finnish (FIN) AF: 0.491 AC: 5190 AN: 10578

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30551 AN: 67972

Other (OTH) AF: 0.470 AC: 990 AN: 2108

Alfa AF: 0.456 Hom.: 8406

Bravo AF: 0.468

Asia WGS AF: 0.482 AC: 1676 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-0.27
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: rs2265477; hg19: chr6-146212338;