1-181049100-A-G

Position:

• chr1-181049100-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001385161.1(MR1):​c.116A>G​(p.His39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,613,918 control chromosomes in the GnomAD database, including 22,152 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2024 hom., cov: 33)
  • Exomes 𝑓: 0.16 (20128 hom.)
• Consequence: MR1 NM_001385161.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.133

Genes affected

MR1 (HGNC:4975): (major histocompatibility complex, class I-related) MAIT (mucosal-associated invariant T-cells) lymphocytes represent a small population of T-cells primarily found in the gut. The protein encoded by this gene is an antigen-presenting molecule that presents metabolites of microbial vitamin B to MAITs. This presentation may activate the MAITs to regulate the amounts of specific types of bacteria in the gut. Several transcript variants encoding different isoforms have been found for this gene, and a pseudogene of it has been detected about 36 kbp upstream on the same chromosome. [provided by RefSeq, Jul 2015]

MR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014429599).
• BP6: Variant 1-181049100-A-G is Benign according to our data. Variant chr1-181049100-A-G is described in ClinVar as [Benign]. Clinvar id is 129620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MR1	NM_001385161.1	c.116A>G	p.His39Arg	missense_variant	2/6	ENST00000367580.6	NP_001372090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MR1	ENST00000367580.6	c.116A>G	p.His39Arg	missense_variant	2/6	1	NM_001385161.1	ENSP00000356552.5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24055 AN: 152130 Hom.: 2029 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.177 AC: 44487 AN: 251116 Hom.: 4539 AF XY: 0.173 AC XY: 23469 AN XY: 135740

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.349

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.160 AC: 233456 AN: 1461670 Hom.: 20128 Cov.: 33 AF XY: 0.160 AC XY: 116469 AN XY: 727150

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.158 AC: 24049 AN: 152248 Hom.: 2024 Cov.: 33 AF XY: 0.159 AC XY: 11865 AN XY: 74418

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.134

Alfa AF: 0.151 Hom.: 959

Bravo AF: 0.162

TwinsUK AF: 0.144 AC: 534

ALSPAC AF: 0.152 AC: 587

ESP6500AA AF: 0.135 AC: 593

ESP6500EA AF: 0.156 AC: 1339

ExAC AF: 0.173 AC: 20992

Asia WGS AF: 0.220 AC: 763 AN: 3478

EpiCase AF: 0.141

EpiControl AF: 0.142

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.1
DANN	Benign	0.30
DEOGEN2	Benign	0.030	.;T;.;.;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.57	T;T;T;T;.;.
MetaRNN	Benign	0.014	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.68	N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.27	.;.;N;N;N;N
REVEL	Benign	0.042
Sift	Benign	1.0	.;.;T;T;T;T
Sift4G	Benign	0.97	T;T;T;T;T;T
Polyphen		0.59	P;P;.;P;P;P
Vest4		0.093
MPC		0.039
ClinPred		0.0082	T
GERP RS		-6.8
Varity_R		0.17
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236410; hg19: chr1-181018236; COSMIC: COSV51580305;