rs16999684

Variant names:

• chr22-48671066-A-C
• rs16999684
• NM_001082967.3:c.262+24320A>C

Variant summary

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

The NM_001082967.3(TAFA5):​c.262+24320A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,092 control chromosomes in the GnomAD database, including 9,954 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 0.33 (9954 hom., cov: 33)
• Consequence: TAFA5 NM_001082967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.262+24320A>C		intron_variant	Intron 2 of 3	ENST00000402357.6	NP_001076436.1
TAFA5	NM_015381.7	c.241+24320A>C		intron_variant	Intron 2 of 3		NP_056196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000402357.6	c.262+24320A>C		intron_variant	Intron 2 of 3	1	NM_001082967.3	ENSP00000383933.2
TAFA5	ENST00000336769.9	c.262+24320A>C		intron_variant	Intron 2 of 3	4		ENSP00000336812.5
TAFA5	ENST00000358295.9	c.241+24320A>C		intron_variant	Intron 2 of 3	2		ENSP00000351043.5
TAFA5	ENST00000473898.1	n.120-36651A>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49474 AN: 151974 Hom.: 9933 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.326 AC: 49547 AN: 152092 Hom.: 9954 Cov.: 33 AF XY: 0.322 AC XY: 23968 AN XY: 74372

African (AFR) AF: 0.577 AC: 23903 AN: 41458

American (AMR) AF: 0.226 AC: 3451 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1116 AN: 5176

South Asian (SAS) AF: 0.327 AC: 1575 AN: 4816

European-Finnish (FIN) AF: 0.243 AC: 2575 AN: 10594

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15402 AN: 67982

Other (OTH) AF: 0.305 AC: 644 AN: 2110

Alfa AF: 0.273 Hom.: 4133

Bravo AF: 0.334

Asia WGS AF: 0.298 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.0
DANN	Benign	0.68
PhyloP100		-0.033
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16999684; hg19: chr22-49066878;