rs738559

Variant names:

• chr22-46113232-G-A
• rs738559
• XM_047441694.1:c.*8643G>A

Variant summary

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

The ENST00000360737.4(MIRLET7BHG):​n.3864G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 179,072 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (138 hom., cov: 33)
  • Exomes 𝑓: 0.038 (42 hom.)
• Consequence: MIRLET7BHG ENST00000360737.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• Publications: 4 publications found

Genes affected

LOC124905135 (HGNC:):

MIRLET7BHG (HGNC:37189): (MIRLET7B host gene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360737.4. 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
	MIRLET7BHG	NR_027033.2		n.4021G>A		non_coding_transcript_exon	Exon 6 of 6
	MIRLET7BHG	NR_110479.1		n.3870G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIRLET7BHG	ENST00000360737.4	TSL:2	n.3864G>A		non_coding_transcript_exon	Exon 5 of 5
	MIRLET7BHG	ENST00000794300.1		n.1092G>A		non_coding_transcript_exon	Exon 6 of 6
	MIRLET7BHG	ENST00000794301.1		n.973G>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5572 AN: 152218 Hom.: 138 Cov.: 33

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0591

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0198

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0379 AC: 1012 AN: 26736 Hom.: 42 Cov.: 0 AF XY: 0.0352 AC XY: 500 AN XY: 14208

African (AFR) AF: 0.00701 AC: 3 AN: 428

American (AMR) AF: 0.0720 AC: 186 AN: 2584

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 7 AN: 562

East Asian (EAS) AF: 0.00 AC: 0 AN: 976

South Asian (SAS) AF: 0.0169 AC: 67 AN: 3976

European-Finnish (FIN) AF: 0.0326 AC: 34 AN: 1042

Middle Eastern (MID) AF: 0.00781 AC: 1 AN: 128

European-Non Finnish (NFE) AF: 0.0434 AC: 680 AN: 15658

Other (OTH) AF: 0.0246 AC: 34 AN: 1382

GnomAD4 genome AF: 0.0366 AC: 5568 AN: 152336 Hom.: 138 Cov.: 33 AF XY: 0.0354 AC XY: 2641 AN XY: 74500

African (AFR) AF: 0.0105 AC: 437 AN: 41582

American (AMR) AF: 0.0588 AC: 900 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4834

European-Finnish (FIN) AF: 0.0395 AC: 420 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0517 AC: 3516 AN: 68022

Other (OTH) AF: 0.0308 AC: 65 AN: 2110

Alfa AF: 0.0389 Hom.: 68

Bravo AF: 0.0382

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.81
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs738559;

hg19: chr22-46509112;