NM_145865.3:c.*756G>T

Variant names:

• chr16-21251576-G-T
• rs7191909
• NM_145865.3:c.*756G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

CRYM Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 40

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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 = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145865.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS4B	NM_145865.3	MANE Select	c.*756G>T		3_prime_UTR	Exon 2 of 2	NP_665872.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS4B	ENST00000311620.7	TSL:1 MANE Select	c.*756G>T		3_prime_UTR	Exon 2 of 2	ENSP00000308772.5
	CRYM	ENST00000574448.5	TSL:1	n.*521-7508C>A		intron	N/A	ENSP00000459982.1
	CRYM	ENST00000570401.5	TSL:5	c.262+7213C>A		intron	N/A	ENSP00000460820.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.214 AC: 3 AN: 14

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.309 AC: 12837 AN: 41478

American (AMR) AF: 0.200 AC: 3054 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3468

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5180

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3074 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16951 AN: 68004

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.216 Hom.: 1470

Bravo AF: 0.244

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.73
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: rs7191909; hg19: chr16-21262897;