11-74848401-G-C

Variant names:

• chr11-74848401-G-C
• rs4944960
• NM_001378157.1:c.1442C>G

Variant summary

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

The NM_001378157.1(XRRA1):​c.1442C>G​(p.Thr481Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,613,084 control chromosomes in the GnomAD database, including 69,795 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6012 hom., cov: 31)
  • Exomes 𝑓: 0.28 (63783 hom.)
• Consequence: XRRA1 NM_001378157.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 37 publications found

Genes affected

XRRA1 (HGNC:18868): (X-ray radiation resistance associated 1) Involved in response to X-ray. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.643002E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378157.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRRA1	NM_001378157.1	MANE Select	c.1442C>G	p.Thr481Arg	missense	Exon 15 of 19	NP_001365086.1
	XRRA1	NM_182969.4		c.1418C>G	p.Thr473Arg	missense	Exon 15 of 19	NP_892014.1
	XRRA1	NM_001378158.1		c.1397C>G	p.Thr466Arg	missense	Exon 14 of 18	NP_001365087.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRRA1	ENST00000684022.1	MANE Select	c.1442C>G	p.Thr481Arg	missense	Exon 15 of 19	ENSP00000507107.1
	XRRA1	ENST00000527087.5	TSL:1	c.1157C>G	p.Thr386Arg	missense	Exon 12 of 15	ENSP00000435838.1
	XRRA1	ENST00000321448.12	TSL:1	c.593C>G	p.Thr198Arg	missense	Exon 12 of 16	ENSP00000319303.8

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40026 AN: 151934 Hom.: 6007 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.305 AC: 74991 AN: 245974 AF XY: 0.287

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.538

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.541

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.283 AC: 412761 AN: 1461032 Hom.: 63783 Cov.: 39 AF XY: 0.275 AC XY: 200107 AN XY: 726778

African (AFR) AF: 0.155 AC: 5190 AN: 33480

American (AMR) AF: 0.530 AC: 23643 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 4605 AN: 26128

East Asian (EAS) AF: 0.557 AC: 22082 AN: 39670

South Asian (SAS) AF: 0.118 AC: 10202 AN: 86220

European-Finnish (FIN) AF: 0.332 AC: 17706 AN: 53354

Middle Eastern (MID) AF: 0.114 AC: 659 AN: 5768

European-Non Finnish (NFE) AF: 0.281 AC: 312753 AN: 1111478

Other (OTH) AF: 0.264 AC: 15921 AN: 60352

GnomAD4 genome AF: 0.263 AC: 40052 AN: 152052 Hom.: 6012 Cov.: 31 AF XY: 0.267 AC XY: 19821 AN XY: 74332

African (AFR) AF: 0.167 AC: 6936 AN: 41492

American (AMR) AF: 0.405 AC: 6191 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2734 AN: 5140

South Asian (SAS) AF: 0.116 AC: 561 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3469 AN: 10574

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18927 AN: 67974

Other (OTH) AF: 0.236 AC: 498 AN: 2110

Alfa AF: 0.256 Hom.: 3374

Bravo AF: 0.274

TwinsUK AF: 0.281 AC: 1042

ALSPAC AF: 0.289 AC: 1114

ESP6500AA AF: 0.161 AC: 663

ESP6500EA AF: 0.263 AC: 2197

ExAC AF: 0.291 AC: 35194

Asia WGS AF: 0.281 AC: 974 AN: 3478

EpiCase AF: 0.262

EpiControl AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.3
DANN	Benign	0.96
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.00016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.0020
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.099
Sift	Benign	0.099	T
Sift4G	Benign	0.39	T
Polyphen		0.69	P
Vest4		0.10
MPC		0.049
ClinPred		0.0044	T
GERP RS		-4.1
Varity_R		0.054
gMVP		0.33
Mutation Taster		=97/3	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: rs4944960; hg19: chr11-74559446; COSMIC: COSV58498289; COSMIC: COSV58498289;