rs4707385

Variant names:

• chr6-87689000-T-C
• rs4707385
• NM_018064.4:c.236-7237A>G

Variant summary

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

The NM_018064.4(AKIRIN2):​c.236-7237A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,102 control chromosomes in the GnomAD database, including 6,729 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 0.29 (6729 hom., cov: 32)
• Consequence: AKIRIN2 NM_018064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 11 publications found

Genes affected

AKIRIN2 (HGNC:21407): (akirin 2) Enables enzyme binding activity and identical protein binding activity. Predicted to be involved in positive regulation of innate immune response and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of interleukin-6 production and response to lipopolysaccharide. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKIRIN2	NM_018064.4	c.236-7237A>G		intron_variant	Intron 1 of 4	ENST00000257787.6	NP_060534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKIRIN2	ENST00000257787.6	c.236-7237A>G		intron_variant	Intron 1 of 4	1	NM_018064.4	ENSP00000257787.5

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44065 AN: 151984 Hom.: 6722 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.290 AC: 44083 AN: 152102 Hom.: 6729 Cov.: 32 AF XY: 0.291 AC XY: 21623 AN XY: 74354

African (AFR) AF: 0.203 AC: 8432 AN: 41510

American (AMR) AF: 0.398 AC: 6082 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1545 AN: 5176

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4824

European-Finnish (FIN) AF: 0.305 AC: 3221 AN: 10570

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21000 AN: 67958

Other (OTH) AF: 0.294 AC: 621 AN: 2112

Alfa AF: 0.308 Hom.: 12838

Bravo AF: 0.293

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.89
PhyloP100		0.17
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: rs4707385; hg19: chr6-88398718; COSMIC: COSV57637410;