rs460271

Variant names:

• chr5-132294369-C-G
• rs460271
• ENST00000471826.1:n.138+809G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132294369-C-G
• chr5-132294369-C-A
• chr5-132294369-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000897522.1(SLC22A4):​c.-248C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 553,534 control chromosomes in the GnomAD database, including 131,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (40095 hom., cov: 31)
  • Exomes 𝑓: 0.67 (91005 hom.)
• Consequence: SLC22A4 ENST00000897522.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.27
• Publications: 10 publications found

Genes affected

P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

SLC22A4 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-132294369-C-G is Benign according to our data. Variant chr5-132294369-C-G is described in ClinVar as Benign. ClinVar VariationId is 1249318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000897522.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	NM_003059.3	MANE Select	c.-248C>G		upstream_gene	N/A	NP_003050.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P4HA2	ENST00000471826.1	TSL:1	n.138+809G>C		intron	N/A
	SLC22A4	ENST00000897522.1		c.-248C>G		5_prime_UTR	Exon 1 of 6	ENSP00000567581.1
	P4HA2	ENST00000431054.5	TSL:4	c.78+809G>C		intron	N/A	ENSP00000391257.1	E7EPI9

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109178 AN: 151820 Hom.: 40046 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.665 AC: 267187 AN: 401594 Hom.: 91005 AF XY: 0.652 AC XY: 137457 AN XY: 210688

African (AFR) AF: 0.852 AC: 9517 AN: 11176

American (AMR) AF: 0.719 AC: 10795 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 8966 AN: 12432

East Asian (EAS) AF: 0.639 AC: 17313 AN: 27104

South Asian (SAS) AF: 0.431 AC: 17511 AN: 40590

European-Finnish (FIN) AF: 0.581 AC: 14722 AN: 25324

Middle Eastern (MID) AF: 0.606 AC: 1079 AN: 1780

European-Non Finnish (NFE) AF: 0.700 AC: 171294 AN: 244832

Other (OTH) AF: 0.685 AC: 15990 AN: 23350

GnomAD4 genome AF: 0.719 AC: 109284 AN: 151940 Hom.: 40095 Cov.: 31 AF XY: 0.707 AC XY: 52500 AN XY: 74274

African (AFR) AF: 0.850 AC: 35278 AN: 41506

American (AMR) AF: 0.715 AC: 10930 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2441 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3155 AN: 5088

South Asian (SAS) AF: 0.434 AC: 2085 AN: 4808

European-Finnish (FIN) AF: 0.571 AC: 6042 AN: 10576

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46867 AN: 67896

Other (OTH) AF: 0.719 AC: 1517 AN: 2110

Alfa AF: 0.575 Hom.: 1521

Bravo AF: 0.743

Asia WGS AF: 0.530 AC: 1846 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.55
DANN	Benign	0.53
PhyloP100		-3.3
PromoterAI		0.0034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs460271; hg19: chr5-131630062;