rs2286587

Positions:

• chr17-76688319-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000592148.1(MXRA7):​c.329A>G​(p.His110Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,467,468 control chromosomes in the GnomAD database, including 96,623 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/10 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 0.32 (8216 hom., cov: 33)
  • Exomes 𝑓: 0.36 (88407 hom.)
• Consequence: MXRA7 ENST00000592148.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

Genes affected

MXRA7 (HGNC:7541): (matrix remodeling associated 7) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.235042E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXRA7	NM_198530.4	c.343-143A>G		intron_variant		ENST00000449428.7	NP_940932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MXRA7	ENST00000449428.7	c.343-143A>G		intron_variant		1	NM_198530.4	ENSP00000391466	P2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48699 AN: 152098 Hom.: 8189 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.317

GnomAD3 exomes AF: 0.324 AC: 29127 AN: 89902 Hom.: 4864 AF XY: 0.328 AC XY: 14757 AN XY: 45054

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.160

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.362 AC: 476047 AN: 1315252 Hom.: 88407 Cov.: 45 AF XY: 0.359 AC XY: 230506 AN XY: 641578

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.320 AC: 48768 AN: 152216 Hom.: 8216 Cov.: 33 AF XY: 0.320 AC XY: 23782 AN XY: 74422

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.315

Alfa AF: 0.353 Hom.: 16568

Bravo AF: 0.308

TwinsUK AF: 0.380 AC: 1410

ALSPAC AF: 0.381 AC: 1467

ExAC AF: 0.236 AC: 23520

Asia WGS AF: 0.223 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.34
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.00032	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
Sift4G	Benign	0.44	T
Vest4		0.067
GERP RS		-6.6
gMVP		0.0039

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

Publications

LitVar

Other links and lift over

dbSNP: rs2286587; hg19: chr17-74684401; COSMIC: COSV63320965;