rs7191909

chr16-21251576-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145865.3(ANKS4B):c.*756G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,152 control chromosomes in the GnomAD database, including 5,131 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 0.25 (5131 hom., cov: 32)
  • Exomes 𝑓: 0.22 (0 hom.)
• Consequence: ANKS4B NM_145865.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

ANKS4B (HGNC:26795): (ankyrin repeat and sterile alpha motif domain containing 4B) Involved in brush border assembly; cellular protein-containing complex assembly; and protein localization to microvillus. Located in brush border and microvillus. [provided by Alliance of Genome Resources, Apr 2022]

CRYM (HGNC:2418): (crystallin mu) Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. Mutations in this gene have been associated with autosomal dominant non-syndromic deafness. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -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 = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS4B	NM_145865.3	c.*756G>T		3_prime_UTR_variant	2/2	ENST00000311620.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS4B	ENST00000311620.7	c.*756G>T		3_prime_UTR_variant	2/2	1	NM_145865.3	P1
CRYM	ENST00000574448.5	c.*521-7508C>A		intron_variant, NMD_transcript_variant		1
CRYM	ENST00000570401.5	c.264+7213C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38395 AN: 152016 Hom.: 5131 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.222 AC: 4 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.252 AC: 38408 AN: 152134 Hom.: 5131 Cov.: 32 AF XY: 0.253 AC XY: 18799 AN XY: 74364

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.200

Alfa AF: 0.189 Hom.: 744

Bravo AF: 0.244

Asia WGS AF: 0.116 AC: 405 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	0.84
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs7191909; hg19: chr16-21262897;