chr7-39609676-G-A

Position:

• chr7-39609676-G-A

Variant summary

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

The NM_001282446.2(YAE1):​c.311G>A​(p.Gly104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,535,508 control chromosomes in the GnomAD database, including 35,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 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 0.27 (7232 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27975 hom.)
• Consequence: YAE1 NM_001282446.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

YAE1 (HGNC:24857): (YAE1 maturation factor of ABCE1) Involved in protein maturation by [4Fe-4S] cluster transfer. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000231951 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1658371E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YAE1	NM_001282446.2	c.311G>A	p.Gly104Glu	missense_variant	3/3		NP_001269375.1
LOC646999		n.39609676G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YAE1	ENST00000432096.2	c.311G>A	p.Gly104Glu	missense_variant	3/3	2		ENSP00000395777.2
ENSG00000231951	ENST00000420748.1	n.499C>T		non_coding_transcript_exon_variant	2/2	4
ENSG00000106540	ENST00000446267.1	n.-41G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41090 AN: 152064 Hom.: 7206 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.196 AC: 25628 AN: 130650 Hom.: 2957 AF XY: 0.187 AC XY: 13374 AN XY: 71330

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.193 AC: 267045 AN: 1383326 Hom.: 27975 Cov.: 33 AF XY: 0.190 AC XY: 129841 AN XY: 682550

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.271 AC: 41167 AN: 152182 Hom.: 7232 Cov.: 33 AF XY: 0.265 AC XY: 19750 AN XY: 74402

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.227

Alfa AF: 0.171 Hom.: 1340

Bravo AF: 0.289

TwinsUK AF: 0.190 AC: 704

ALSPAC AF: 0.182 AC: 700

ExAC AF: 0.132 AC: 1827

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.84
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00030	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.00012	T
MetaSVM	Benign	-0.93	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.024
Sift	Benign	0.18	T
Sift4G	Benign	1.0	T
Vest4		0.012
ClinPred		0.0019	T
GERP RS		-1.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4723884; hg19: chr7-39649275; COSMIC: COSV69296587; COSMIC: COSV69296587;