dbSNP rs10876469: ATF7:c.-162A>C (chr12-53626419-T-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_006856.3(ATF7):c.-162A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,466 control chromosomes in the GnomAD database, including 10,111 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 0.36 ( 10084 hom., cov: 32)

Exomes 𝑓: 0.30 ( 27 hom. )

Consequence

ATF7
NM_006856.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0760

Publications

8 publications found

Variant links:

COSMIC-nc: COSV69392993

Genes affected

ATF7 (HGNC:792): (activating transcription factor 7) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; mitogen-activated protein kinase binding activity; and transcription coactivator binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Biomarker of colorectal cancer. [provided by Alliance of Genome Resources, Apr 2022]

ATF7 links:

ATF7-NPFF (HGNC:55073): (ATF7-NPFF readthrough) Predicted to enable DNA binding activity and DNA-binding transcription factor activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ATF7-NPFF links:

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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=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006856.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATF7	NM_006856.3	MANE Select	c.-162A>C	upstream_gene	N/A	NP_006847.1	P17544-6
ATF7	NM_001366555.2		c.-162A>C	upstream_gene	N/A	NP_001353484.1	P17544-1
ATF7-NPFF	NM_001366559.1		c.-162A>C	upstream_gene	N/A	NP_001353488.1	K7ELQ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATF7	ENST00000420353.7	TSL:1 MANE Select	c.-162A>C	upstream_gene	N/A	ENSP00000399465.1	P17544-6
ATF7	ENST00000591397.1	TSL:1	c.-162A>C	upstream_gene	N/A	ENSP00000465192.1	P17544-5
ATF7	ENST00000923853.1		c.-162A>C	upstream_gene	N/A	ENSP00000593912.1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54233

AN:

151718

Hom.:

10075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.369

GnomAD4 exome

AF:

0.305

AC:

192

AN:

630

Hom.:

Cov.:

AF XY:

0.320

AC XY:

132

AN XY:

412

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.318

AC:

136

AN:

428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.285

AC:

AN:

172

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.358

AC:

54283

AN:

151836

Hom.:

10084

Cov.:

AF XY:

0.364

AC XY:

27010

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.368

AC:

15228

AN:

41398

American (AMR)

AF:

0.413

AC:

6297

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1202

AN:

3470

East Asian (EAS)

AF:

0.709

AC:

3653

AN:

5154

South Asian (SAS)

AF:

0.425

AC:

2040

AN:

4804

European-Finnish (FIN)

AF:

0.350

AC:

3668

AN:

10486

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

21002

AN:

67948

Other (OTH)

AF:

0.366

AC:

774

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1839

3678

5518

7357

9196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.324

Hom.:

9869

Bravo

AF:

0.364

Asia WGS

AF:

0.534

AC:

1854

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.6

(source)

DANN

Benign

0.66

PhyloP100

0.076

PromoterAI

0.031

Neutral

(source)

Splicing

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