rs2265919

Variant names:

• chr6-145900617-A-G
• rs2265919
• NM_001042683.3:c.4516-5640T>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.4516-5640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,782 control chromosomes in the GnomAD database, including 10,920 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 (10920 hom., cov: 30)
• Consequence: SHPRH NM_001042683.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 7 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 = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHPRH	NM_001042683.3	c.4516-5640T>C		intron_variant	Intron 25 of 29	ENST00000275233.12	NP_001036148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHPRH	ENST00000275233.12	c.4516-5640T>C		intron_variant	Intron 25 of 29	1	NM_001042683.3	ENSP00000275233.7

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56176 AN: 151662 Hom.: 10904 Cov.: 30

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.433

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: 0.370 AC: 56210 AN: 151782 Hom.: 10920 Cov.: 30 AF XY: 0.373 AC XY: 27699 AN XY: 74174

African (AFR) AF: 0.271 AC: 11222 AN: 41410

American (AMR) AF: 0.287 AC: 4373 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3466

East Asian (EAS) AF: 0.352 AC: 1813 AN: 5148

South Asian (SAS) AF: 0.491 AC: 2359 AN: 4804

European-Finnish (FIN) AF: 0.481 AC: 5066 AN: 10530

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28583 AN: 67868

Other (OTH) AF: 0.378 AC: 797 AN: 2110

Alfa AF: 0.407 Hom.: 6724

Bravo AF: 0.350

Asia WGS AF: 0.450 AC: 1562 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.50
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: rs2265919; hg19: chr6-146221753;