rs183441

Variant names:

• chr16-21267023-C-A
• rs183441
• NM_001376256.1:c.673+531G>T

Variant summary

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

The NM_001376256.1(CRYM):​c.673+531G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 151,850 control chromosomes in the GnomAD database, including 55 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 0.017 (55 hom., cov: 31)
• Consequence: CRYM NM_001376256.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 1 publications found

Genes affected

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

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

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss 40

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376256.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYM	NM_001376256.1	MANE Select	c.673+531G>T		intron	N/A	NP_001363185.1	Q14894
	CRYM	NM_001888.5		c.673+531G>T		intron	N/A	NP_001879.1	Q14894

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYM	ENST00000572914.2	TSL:2 MANE Select	c.673+531G>T		intron	N/A	ENSP00000461904.2	Q14894
	CRYM	ENST00000219599.8	TSL:1	c.673+531G>T		intron	N/A	ENSP00000219599.3	Q14894
	CRYM	ENST00000574448.5	TSL:1	n.*313+531G>T		intron	N/A	ENSP00000459982.1	I3L2W5

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2524 AN: 151734 Hom.: 54 Cov.: 31

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00729

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00766

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

GnomAD4 genome AF: 0.0168 AC: 2546 AN: 151850 Hom.: 55 Cov.: 31 AF XY: 0.0160 AC XY: 1188 AN XY: 74226

African (AFR) AF: 0.0579 AC: 2398 AN: 41420

American (AMR) AF: 0.00728 AC: 111 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000236 AC: 16 AN: 67930

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.0126 Hom.: 7

Bravo AF: 0.0186

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.28
DANN	Benign	0.39
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs183441; hg19: chr16-21278344;