rs2265917

Variant names:

• chr6-145891149-A-G
• rs2265917
• NM_001042683.3:c.4874+2066T>C

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+2066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,952 control chromosomes in the GnomAD database, including 10,964 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 0.37 (10964 hom., cov: 31)
• Consequence: SHPRH NM_001042683.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHPRH	NM_001042683.3	c.4874+2066T>C		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+2066T>C		intron_variant	Intron 28 of 29	1	NM_001042683.3	ENSP00000275233.7

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56285 AN: 151832 Hom.: 10948 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.371 AC: 56319 AN: 151952 Hom.: 10964 Cov.: 31 AF XY: 0.374 AC XY: 27747 AN XY: 74268

African (AFR) AF: 0.271 AC: 11234 AN: 41440

American (AMR) AF: 0.288 AC: 4391 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1441 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1808 AN: 5148

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4820

European-Finnish (FIN) AF: 0.482 AC: 5075 AN: 10538

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28642 AN: 67956

Other (OTH) AF: 0.377 AC: 798 AN: 2114

Alfa AF: 0.407 Hom.: 6731

Bravo AF: 0.350

Asia WGS AF: 0.451 AC: 1566 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	0.23
DANN	Benign	0.35
PhyloP100		-0.51
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: rs2265917; hg19: chr6-146212285;