dbSNP rs9306895: GDF7:c.*6968T>C (chr2-20678393-T-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_182828.4(GDF7):c.*6968T>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 0.3 in 152,270 control chromosomes in the GnomAD database, including 8,046 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 0.30 ( 8046 hom., cov: 34)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

GDF7
NM_182828.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.549

Publications

21 publications found

Variant links:

Genes affected

GDF7 (HGNC:4222): (growth differentiation factor 7) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein may play a role in the differentiation of tendon cells and spinal cord interneurons. A mutation in this gene may be associated with increased risk for Barrett's esophagus and esophageal adenocarcinoma. [provided by RefSeq, Sep 2016]

GDF7 links:

ENSG00000270100 (HGNC:):

ENSG00000270100 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF7	NM_182828.4 link	c.*6968T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000272224.5	NP_878248.2	Q7Z4P5Q75RY1
GDF7	XM_047443522.1 link	c.*6968T>C		3_prime_UTR_variant	Exon 2 of 2		XP_047299478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF7	ENST00000272224.5 link	c.*6968T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_182828.4	ENSP00000272224.3		Q7Z4P5
ENSG00000270100	ENST00000602445.1 link	n.540A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45629

AN:

152150

Hom.:

8039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.300

AC:

45633

AN:

152266

Hom.:

8046

Cov.:

AF XY:

0.303

AC XY:

22549

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.108

AC:

4481

AN:

41572

American (AMR)

AF:

0.346

AC:

5295

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1371

AN:

3470

East Asian (EAS)

AF:

0.472

AC:

2445

AN:

5182

South Asian (SAS)

AF:

0.369

AC:

1779

AN:

4826

European-Finnish (FIN)

AF:

0.362

AC:

3835

AN:

10594

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25188

AN:

68004

Other (OTH)

AF:

0.357

AC:

755

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1574

3148

4721

6295

7869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.354

Hom.:

4311

Bravo

AF:

0.286

Asia WGS

AF:

0.417

AC:

1451

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.8

(source)

DANN

Benign

0.80

PhyloP100

-0.55

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