1-181049100-A-G

Variant names:

• chr1-181049100-A-G
• rs2236410
• NM_001385161.1:c.116A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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
• Publications: 29 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385161.1. 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
	MR1	NM_001385161.1	MANE Select	c.116A>G	p.His39Arg	missense	Exon 2 of 6	NP_001372090.1	Q95460-1
	MR1	NM_001531.3		c.116A>G	p.His39Arg	missense	Exon 3 of 7	NP_001522.1	Q95460-1
	MR1	NM_001385162.1		c.116A>G	p.His39Arg	missense	Exon 2 of 6	NP_001372091.1	A0A8C8PVM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MR1	ENST00000367580.6	TSL:1 MANE Select	c.116A>G	p.His39Arg	missense	Exon 2 of 6	ENSP00000356552.5	Q95460-1
	MR1	ENST00000367579.7	TSL:1	c.116A>G	p.His39Arg	missense	Exon 2 of 6	ENSP00000356551.3	Q95460-2
	MR1	ENST00000282990.10	TSL:1	c.116A>G	p.His39Arg	missense	Exon 2 of 5	ENSP00000282990.6	Q95460-3

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

GnomAD2 exomes AF: 0.177 AC: 44487 AN: 251116 AF XY: 0.173

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 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

African (AFR) AF: 0.134 AC: 4491 AN: 33472

American (AMR) AF: 0.239 AC: 10684 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3436 AN: 26132

East Asian (EAS) AF: 0.360 AC: 14295 AN: 39698

South Asian (SAS) AF: 0.174 AC: 15003 AN: 86252

European-Finnish (FIN) AF: 0.144 AC: 7685 AN: 53418

Middle Eastern (MID) AF: 0.0861 AC: 496 AN: 5762

European-Non Finnish (NFE) AF: 0.151 AC: 167640 AN: 1111856

Other (OTH) AF: 0.161 AC: 9726 AN: 60382

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

African (AFR) AF: 0.133 AC: 5509 AN: 41550

American (AMR) AF: 0.213 AC: 3262 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1792 AN: 5172

South Asian (SAS) AF: 0.178 AC: 859 AN: 4830

European-Finnish (FIN) AF: 0.140 AC: 1485 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10233 AN: 68008

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.148 Hom.: 1077

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.68	N
PhyloP100		-0.13
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	0.97	T
Polyphen		0.59	P
Vest4		0.093
MPC		0.039
ClinPred		0.0082	T
GERP RS		-6.8
Varity_R		0.17
gMVP		0.59
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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