chr6-106512825-G-A

Variant names:

• chr6-106512825-G-A
• rs773473919
• NM_001371242.2:c.1708G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371242.2(CRYBG1):​c.1708G>A​(p.Glu570Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,576,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89
• Publications: 1 publications found

Genes affected

CRYBG1 (HGNC:356): (crystallin beta-gamma domain containing 1) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000300544 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12869582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG1	NM_001371242.2	c.1708G>A	p.Glu570Lys	missense_variant	Exon 3 of 22	ENST00000633556.3	NP_001358171.1
CRYBG1	NM_001624.4	c.484G>A	p.Glu162Lys	missense_variant	Exon 1 of 20		NP_001615.2
CRYBG1	XM_047418270.1	c.1786G>A	p.Glu596Lys	missense_variant	Exon 4 of 23		XP_047274226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBG1	ENST00000633556.3	c.1708G>A	p.Glu570Lys	missense_variant	Exon 3 of 22	5	NM_001371242.2	ENSP00000488010.2
CRYBG1	ENST00000651520.1	c.1549G>A	p.Glu517Lys	missense_variant	Exon 2 of 2			ENSP00000499126.1
ENSG00000300544	ENST00000772631.1	n.153C>T		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000977 AC: 18 AN: 184328 AF XY: 0.0000997

Gnomad AFR exome AF: 0.000103

Gnomad AMR exome AF: 0.000106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000157

Gnomad OTH exome AF: 0.000415

GnomAD4 exome AF: 0.0000569 AC: 81 AN: 1424166 Hom.: 0 Cov.: 36 AF XY: 0.0000539 AC XY: 38 AN XY: 704866

African (AFR) AF: 0.00 AC: 0 AN: 32680

American (AMR) AF: 0.0000759 AC: 3 AN: 39510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25420

East Asian (EAS) AF: 0.00 AC: 0 AN: 37726

South Asian (SAS) AF: 0.00 AC: 0 AN: 82116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.0000695 AC: 76 AN: 1092910

Other (OTH) AF: 0.0000340 AC: 2 AN: 58840

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000420 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.484G>A (p.E162K) alteration is located in exon 1 (coding exon 1) of the AIM1 gene. This alteration results from a G to A substitution at nucleotide position 484, causing the glutamic acid (E) at amino acid position 162 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.79	T
PhyloP100		2.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	.;D
Sift4G	Benign	0.28	T;T
Polyphen		0.10	.;B
Vest4		0.37
MVP		0.62
MPC		0.14
ClinPred		0.063	T
GERP RS		4.1
Varity_R		0.19
gMVP		0.31
Mutation Taster		=98/2	polymorphism

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: rs773473919; hg19: chr6-106960700;