chr1-156743859-T-C

Variant names:

• chr1-156743859-T-C
• rs372280917
• NM_004494.3:c.509A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004494.3(HDGF):​c.509A>G​(p.Lys170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: HDGF NM_004494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91
• Publications: 0 publications found

Genes affected

HDGF (HGNC:4856): (heparin binding growth factor) This gene encodes a member of the hepatoma-derived growth factor family. The encoded protein has mitogenic and DNA-binding activity and may play a role in cellular proliferation and differentiation. High levels of expression of this gene enhance the growth of many tumors. This gene was thought initially to be located on chromosome X; however, that location has been determined to correspond to a related pseudogene. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15402442).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004494.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDGF	NM_004494.3	MANE Select	c.509A>G	p.Lys170Arg	missense	Exon 5 of 6	NP_004485.1	P51858-1
	HDGF	NM_001319186.2		c.578A>G	p.Lys193Arg	missense	Exon 5 of 6	NP_001306115.1
	HDGF	NM_001126050.2		c.557A>G	p.Lys186Arg	missense	Exon 5 of 6	NP_001119522.1	P51858-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDGF	ENST00000357325.10	TSL:1 MANE Select	c.509A>G	p.Lys170Arg	missense	Exon 5 of 6	ENSP00000349878.5	P51858-1
	HDGF	ENST00000465180.5	TSL:1	n.923A>G		non_coding_transcript_exon	Exon 7 of 8
	HDGF	ENST00000710272.1		c.764A>G	p.Lys255Arg	missense	Exon 5 of 6	ENSP00000518165.1	A0AA34QVG5

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000483 AC: 12 AN: 248532 AF XY: 0.0000446

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000630

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000120 AC: 175 AN: 1461384 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 88 AN XY: 727028

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000112 AC: 5 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000150 AC: 167 AN: 1111704

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.082
Sift	Benign	0.17	T
Sift4G	Benign	0.23	T
Polyphen		0.95	P
Vest4		0.15
MVP		0.51
MPC		1.1
ClinPred		0.16	T
GERP RS		4.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.067
gMVP		0.24
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs372280917; hg19: chr1-156713651;