dbSNP rs1055375: HOMEZ:c.*2488T>C (chr14-23273087-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020834.3(HOMEZ):c.*2488T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 415,016 control chromosomes in the GnomAD database, including 663 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 0.041 ( 174 hom., cov: 32)

Exomes 𝑓: 0.053 ( 489 hom. )

Consequence

HOMEZ
NM_020834.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

Publications

2 publications found

Variant links:

Genes affected

HOMEZ (HGNC:20164): (homeobox and leucine zipper encoding) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HOMEZ links:

RNF212B (HGNC:20438): (ring finger protein 212B) Predicted to enable SUMO transferase activity. Predicted to be involved in homologous chromosome pairing at meiosis and protein sumoylation. Predicted to be active in synaptonemal complex. [provided by Alliance of Genome Resources, Apr 2022]

RNF212B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMEZ	NM_020834.3 link	c.*2488T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000357460.7	NP_065885.2	Q8IX15-1
RNF212B	NM_001282322.3 link	c.*196A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000430154.7	NP_001269251.1	A8MTL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMEZ	ENST00000357460.7 link	c.*2488T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_020834.3	ENSP00000350049.4		Q8IX15-1
RNF212B	ENST00000430154.7 link	c.*196A>G		3_prime_UTR_variant	Exon 15 of 15	5	NM_001282322.3	ENSP00000397830.2		A8MTL3

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6270

AN:

152168

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0388

Gnomad ASJ

AF:

0.0833

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0191

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0521

GnomAD4 exome

AF:

0.0533

AC:

13995

AN:

262730

Hom.:

489

Cov.:

AF XY:

0.0534

AC XY:

7239

AN XY:

135672

show subpopulations

African (AFR)

AF:

0.0137

AC:

AN:

6810

American (AMR)

AF:

0.0440

AC:

424

AN:

9644

Ashkenazi Jewish (ASJ)

AF:

0.0797

AC:

724

AN:

9086

East Asian (EAS)

AF:

0.0000478

AC:

AN:

20912

South Asian (SAS)

AF:

0.0229

AC:

287

AN:

12544

European-Finnish (FIN)

AF:

0.0229

AC:

454

AN:

19818

Middle Eastern (MID)

AF:

0.110

AC:

160

AN:

1456

European-Non Finnish (NFE)

AF:

0.0661

AC:

10939

AN:

165482

Other (OTH)

AF:

0.0538

AC:

913

AN:

16978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

587

1174

1760

2347

2934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0412

AC:

6268

AN:

152286

Hom.:

174

Cov.:

AF XY:

0.0386

AC XY:

2875

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0118

AC:

492

AN:

41550

American (AMR)

AF:

0.0388

AC:

594

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0833

AC:

289

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0189

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0190

AC:

202

AN:

10616

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0637

AC:

4336

AN:

68030

Other (OTH)

AF:

0.0516

AC:

109

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

307

614

920

1227

1534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0501

Hom.:

Bravo

AF:

0.0420

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.4

(source)

DANN

Benign

0.78

PhyloP100

0.012

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over