rs1472122

Variant names:

• chr3-151316814-G-A
• rs1472122
• NM_023915.4:c.-327C>T

Variant summary

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

The NM_023915.4(GPR87):​c.-327C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,980 control chromosomes in the GnomAD database, including 18,012 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 0.49 (18009 hom., cov: 31)
  • Exomes 𝑓: 0.58 (3 hom.)
• Consequence: GPR87 NM_023915.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 9 publications found

Genes affected

GPR87 (HGNC:4538): (G protein-coupled receptor 87) This gene encodes a G protein-coupled receptor and is located in a cluster of G protein-couple receptor genes on chromosome 3. The encoded protein has been shown to be overexpressed in lung squamous cell carcinoma (PMID:18057535) and regulated by p53 (PMID:19602589). [provided by RefSeq, Nov 2011]

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

MED12L Gene-Disease associations (from GenCC):

• Nizon-Isidor syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR87	NM_023915.4	c.-327C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000260843.5	NP_076404.3
GPR87	NM_023915.4	c.-327C>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000260843.5	NP_076404.3
MED12L	NM_001393769.1	c.2251-33245G>A		intron_variant	Intron 16 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR87	ENST00000260843.5	c.-327C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	NM_023915.4	ENSP00000260843.4
GPR87	ENST00000260843.5	c.-327C>T		5_prime_UTR_variant	Exon 1 of 3	1	NM_023915.4	ENSP00000260843.4
MED12L	ENST00000687756.1	c.2251-33245G>A		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73740 AN: 151838 Hom.: 18004 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.583 AC: 14 AN: 24 Hom.: 3 Cov.: 0 AF XY: 0.591 AC XY: 13 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.550 AC: 11 AN: 20

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.486 AC: 73791 AN: 151956 Hom.: 18009 Cov.: 31 AF XY: 0.484 AC XY: 35927 AN XY: 74260

African (AFR) AF: 0.508 AC: 21027 AN: 41430

American (AMR) AF: 0.506 AC: 7721 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2198 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2579 AN: 5168

South Asian (SAS) AF: 0.514 AC: 2475 AN: 4814

European-Finnish (FIN) AF: 0.402 AC: 4241 AN: 10538

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31864 AN: 67954

Other (OTH) AF: 0.521 AC: 1102 AN: 2116

Alfa AF: 0.488 Hom.: 24039

Bravo AF: 0.496

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.75
PhyloP100		1.4
PromoterAI		0.028	Neutral
Mutation Taster		=300/0	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: rs1472122; hg19: chr3-151034602;