rs4723884

Variant names:

• chr7-39609676-G-A
• rs4723884
• NM_001282446.2:c.311G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-39609676-G-A
• chr7-39609676-G-C

Variant summary

Our verdict is Benign. The variant received -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. 12/15 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
YAE1	NM_001282446.2	c.311G>A	p.Gly104Glu	missense_variant	Exon 3 of 3		NP_001269375.1
LOC646999		n.39609676G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAE1	ENST00000432096.3	c.311G>A	p.Gly104Glu	missense_variant	Exon 3 of 3	2		ENSP00000395777.2
ENSG00000231951	ENST00000420748.1	n.499C>T		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.196 AC: 25628 AN: 130650 AF XY: 0.187

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 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

African (AFR) AF: 0.509 AC: 16093 AN: 31592

American (AMR) AF: 0.247 AC: 8834 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3525 AN: 25180

East Asian (EAS) AF: 0.117 AC: 4169 AN: 35732

South Asian (SAS) AF: 0.136 AC: 10800 AN: 79234

European-Finnish (FIN) AF: 0.153 AC: 5123 AN: 33468

Middle Eastern (MID) AF: 0.150 AC: 855 AN: 5692

European-Non Finnish (NFE) AF: 0.191 AC: 206332 AN: 1078836

Other (OTH) AF: 0.195 AC: 11314 AN: 57892

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

African (AFR) AF: 0.503 AC: 20881 AN: 41504

American (AMR) AF: 0.238 AC: 3637 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3468

East Asian (EAS) AF: 0.114 AC: 587 AN: 5164

South Asian (SAS) AF: 0.137 AC: 661 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1622 AN: 10616

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12563 AN: 67994

Other (OTH) AF: 0.227 AC: 480 AN: 2114

Alfa AF: 0.177 Hom.: 1617

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
AlphaMissense	Benign	0.072
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
PhyloP100		-1.2
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
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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