dbSNP rs1322319: ZNF248:c.-271T>C (chr10-37856581-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 ENST00000611278.4(ZNF248):c.-271T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,142,014 control chromosomes in the GnomAD database, including 11,443 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 0.13 ( 1353 hom., cov: 32)

Exomes 𝑓: 0.14 ( 10090 hom. )

Consequence

ZNF248
ENST00000611278.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.332

Publications

5 publications found

Variant links:

Genes affected

ZNF248 (HGNC:13041): (zinc finger protein 248) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF248 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=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611278.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF248	NM_021045.3	MANE Select	c.-125-49T>C	intron	N/A	NP_066383.1
ZNF248	NM_001352472.2		c.-271T>C	5_prime_UTR	Exon 1 of 4	NP_001339401.1
ZNF248	NM_001352492.2		c.-680T>C	5_prime_UTR	Exon 1 of 6	NP_001339421.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF248	ENST00000611278.4	TSL:1	c.-271T>C	5_prime_UTR	Exon 1 of 5	ENSP00000484191.1
ZNF248	ENST00000395867.8	TSL:1 MANE Select	c.-125-49T>C	intron	N/A	ENSP00000379208.3
ZNF248	ENST00000374648.7	TSL:1	c.-125-49T>C	intron	N/A	ENSP00000363778.3

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19539

AN:

151950

Hom.:

1352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.0628

Gnomad FIN

AF:

0.0916

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.144

GnomAD4 exome

AF:

0.141

AC:

139190

AN:

989946

Hom.:

10090

Cov.:

AF XY:

0.141

AC XY:

65422

AN XY:

465050

show subpopulations

African (AFR)

AF:

0.0927

AC:

1960

AN:

21144

American (AMR)

AF:

0.189

AC:

1256

AN:

6652

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

1542

AN:

11482

East Asian (EAS)

AF:

0.103

AC:

1844

AN:

17854

South Asian (SAS)

AF:

0.0656

AC:

1305

AN:

19898

European-Finnish (FIN)

AF:

0.0760

AC:

729

AN:

9590

Middle Eastern (MID)

AF:

0.144

AC:

347

AN:

2406

European-Non Finnish (NFE)

AF:

0.145

AC:

125273

AN:

863282

Other (OTH)

AF:

0.131

AC:

4934

AN:

37638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

5549

11098

16648

22197

27746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5512

11024

16536

22048

27560

<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:

0.129

AC:

19544

AN:

152068

Hom.:

1353

Cov.:

AF XY:

0.128

AC XY:

9521

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.104

AC:

4298

AN:

41494

American (AMR)

AF:

0.195

AC:

2976

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

489

AN:

3472

East Asian (EAS)

AF:

0.103

AC:

532

AN:

5152

South Asian (SAS)

AF:

0.0624

AC:

301

AN:

4822

European-Finnish (FIN)

AF:

0.0916

AC:

967

AN:

10554

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9524

AN:

67988

Other (OTH)

AF:

0.143

AC:

300

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

820

1640

2459

3279

4099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.131

Hom.:

163

Bravo

AF:

0.139

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over