rs131026

Variant names:

• chr22-48780096-G-A
• rs131026
• ENST00000336769.9:c.391-70662G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-48780096-G-A
• chr22-48780096-G-C
• chr22-48780096-G-T

Variant summary

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

The ENST00000336769.9(TAFA5):​c.391-70662G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,054 control chromosomes in the GnomAD database, including 20,722 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 0.46 (20722 hom., cov: 33)
• Consequence: TAFA5 ENST00000336769.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• Publications: 4 publications found

Genes affected

TAFA5 (HGNC:21592): (TAFA chemokine like family member 5) This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines that act as regulators of immune and nervous cells. [provided by RefSeq, Sep 2013]

MIR4535 (HGNC:41629): (microRNA 4535) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR4535	NR_039761.1	n.-199G>A		upstream_gene_variant
MIR4535	unassigned_transcript_3692	n.-235G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000336769.9	c.391-70662G>A		intron_variant	Intron 3 of 3	4		ENSP00000336812.5
MIR4535	ENST00000580946.1	n.-199G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69628 AN: 151936 Hom.: 20674 Cov.: 33

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.459 AC: 69733 AN: 152054 Hom.: 20722 Cov.: 33 AF XY: 0.460 AC XY: 34207 AN XY: 74322

African (AFR) AF: 0.792 AC: 32892 AN: 41518

American (AMR) AF: 0.324 AC: 4950 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5111 AN: 5158

South Asian (SAS) AF: 0.570 AC: 2745 AN: 4814

European-Finnish (FIN) AF: 0.281 AC: 2969 AN: 10556

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.277 AC: 18799 AN: 67944

Other (OTH) AF: 0.435 AC: 917 AN: 2110

Alfa AF: 0.315 Hom.: 14085

Bravo AF: 0.473

Asia WGS AF: 0.782 AC: 2716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.44
PhyloP100		-3.1

Splicing

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

Other links and lift over

dbSNP: rs131026; hg19: chr22-49175908;