NM_182828.4:c.*7221T>C

Variant names:

• chr2-20678646-T-C
• rs3072
• NM_182828.4:c.*7221T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182828.4(GDF7):​c.*7221T>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 0.304 in 152,248 control chromosomes in the GnomAD database, including 8,294 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 (8293 hom., cov: 33)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: GDF7 NM_182828.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 34 publications found

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]

ENSG00000270100 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF7	NM_182828.4	MANE Select	c.*7221T>C		3_prime_UTR	Exon 2 of 2	NP_878248.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF7	ENST00000272224.5	TSL:1 MANE Select	c.*7221T>C		3_prime_UTR	Exon 2 of 2	ENSP00000272224.3
	ENSG00000270100	ENST00000602445.1	TSL:6	n.287A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46291 AN: 152124 Hom.: 8285 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.304 AC: 46298 AN: 152242 Hom.: 8293 Cov.: 33 AF XY: 0.307 AC XY: 22846 AN XY: 74446

African (AFR) AF: 0.109 AC: 4514 AN: 41554

American (AMR) AF: 0.349 AC: 5329 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2456 AN: 5188

South Asian (SAS) AF: 0.374 AC: 1805 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3853 AN: 10592

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25668 AN: 68008

Other (OTH) AF: 0.366 AC: 774 AN: 2114

Alfa AF: 0.363 Hom.: 21941

Bravo AF: 0.290

Asia WGS AF: 0.420 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.67
DANN	Benign	0.53
PhyloP100		-0.92

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

Other links and lift over

dbSNP: rs3072; hg19: chr2-20878406;