dbSNP rs1036819: ZFAT:c.2475+734T>G (chr8-134599702-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020863.4(ZFAT):c.2475+734T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 439,292 control chromosomes in the GnomAD database, including 3,972 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 0.11 ( 1191 hom., cov: 33)

Exomes 𝑓: 0.13 ( 2781 hom. )

Consequence

ZFAT
NM_020863.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.200

Publications

18 publications found

Variant links:

Genes affected

ZFAT (HGNC:19899): (zinc finger and AT-hook domain containing) This gene encodes a protein that likely binds DNA and functions as a transcriptional regulator involved in apoptosis and cell survival. This gene resides in a susceptibility locus for autoimmune thyroid disease (AITD) on chromosome 8q24. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]

ZFAT links:

ZFAT-AS1 (HGNC:33992): (ZFAT antisense RNA 1) This gene encodes a small antisense RNA that may be involved in regulating the sense strand locus, zinc finger and AT hook domain containing. This RNA may play a role in B cell function. A single nucleotide polymorphism in the promoter of this gene is associated with an increased risk of autoimmune thyroid disease.[provided by RefSeq, Jan 2010]

ZFAT-AS1 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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAT	NM_020863.4 link	c.2475+734T>G		intron_variant	Intron 7 of 15	ENST00000377838.8	NP_065914.2	Q9P243-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8 link	c.2475+734T>G		intron_variant	Intron 7 of 15	1	NM_020863.4	ENSP00000367069.3		Q9P243-1
ZFAT	ENST00000429442.6 link	c.2439+734T>G		intron_variant	Intron 7 of 15	1		ENSP00000394501.2		F8W7M8

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16667

AN:

152190

Hom.:

1186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0715

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0689

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.127

AC:

36446

AN:

286984

Hom.:

2781

Cov.:

AF XY:

0.130

AC XY:

21284

AN XY:

164122

show subpopulations

African (AFR)

AF:

0.0756

AC:

553

AN:

7318

American (AMR)

AF:

0.117

AC:

2566

AN:

21996

Ashkenazi Jewish (ASJ)

AF:

0.0729

AC:

723

AN:

9920

East Asian (EAS)

AF:

0.388

AC:

3527

AN:

9086

South Asian (SAS)

AF:

0.145

AC:

8055

AN:

55520

European-Finnish (FIN)

AF:

0.122

AC:

1491

AN:

12174

Middle Eastern (MID)

AF:

0.197

AC:

527

AN:

2680

European-Non Finnish (NFE)

AF:

0.112

AC:

17320

AN:

154758

Other (OTH)

AF:

0.124

AC:

1684

AN:

13532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1644

3289

4933

6578

8222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.110

AC:

16692

AN:

152308

Hom.:

1191

Cov.:

AF XY:

0.111

AC XY:

8287

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0717

AC:

2982

AN:

41584

American (AMR)

AF:

0.102

AC:

1563

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0689

AC:

239

AN:

3470

East Asian (EAS)

AF:

0.379

AC:

1961

AN:

5174

South Asian (SAS)

AF:

0.148

AC:

714

AN:

4816

European-Finnish (FIN)

AF:

0.121

AC:

1280

AN:

10616

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7494

AN:

68028

Other (OTH)

AF:

0.125

AC:

264

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

732

1463

2195

2926

3658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.165

Hom.:

16807

Bravo

AF:

0.110

Asia WGS

AF:

0.209

AC:

725

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.9

(source)

DANN

Benign

0.85

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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