Genetic Variant HES7:c.*131G>T (chr17-8121440-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001165967.2(HES7):c.*131G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 610,010 control chromosomes in the GnomAD database, including 1,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 637 hom., cov: 32)

Exomes 𝑓: 0.022 ( 596 hom. )

Consequence

HES7
NM_001165967.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.62

Publications

2 publications found

Variant links:

Genes affected

HES7 (HGNC:15977): (hes family bHLH transcription factor 7) This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

HES7 Gene-Disease associations (from GenCC):

spondylocostal dysostosis 4, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HES7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-8121440-C-A is Benign according to our data. Variant chr17-8121440-C-A is described in ClinVar as Benign. ClinVar VariationId is 1239596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165967.2. 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
	HES7	NM_001165967.2	MANE Select	c.*131G>T		3_prime_UTR	Exon 4 of 4	NP_001159439.1	Q9BYE0-2
	HES7	NM_032580.4		c.*131G>T		3_prime_UTR	Exon 4 of 4	NP_115969.2	Q9BYE0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HES7	ENST00000541682.7	TSL:1 MANE Select	c.*131G>T		3_prime_UTR	Exon 4 of 4	ENSP00000446205.2	Q9BYE0-2
	HES7	ENST00000317814.8	TSL:1	c.*131G>T		downstream_gene	N/A	ENSP00000314774.4	Q9BYE0-1

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9409

AN:

152142

Hom.:

633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0476

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0610

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.0497

GnomAD4 exome

AF:

0.0220

AC:

10092

AN:

457750

Hom.:

596

Cov.:

AF XY:

0.0217

AC XY:

4910

AN XY:

226338

show subpopulations

African (AFR)

AF:

0.149

AC:

1578

AN:

10584

American (AMR)

AF:

0.0568

AC:

440

AN:

7748

Ashkenazi Jewish (ASJ)

AF:

0.0350

AC:

385

AN:

11006

East Asian (EAS)

AF:

0.166

AC:

3937

AN:

23702

South Asian (SAS)

AF:

0.0557

AC:

602

AN:

10810

European-Finnish (FIN)

AF:

0.0403

AC:

899

AN:

22334

Middle Eastern (MID)

AF:

0.0190

AC:

AN:

1838

European-Non Finnish (NFE)

AF:

0.00347

AC:

1200

AN:

345528

Other (OTH)

AF:

0.0420

AC:

1016

AN:

24200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

536

1071

1607

2142

2678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.0620

AC:

9433

AN:

152260

Hom.:

637

Cov.:

AF XY:

0.0644

AC XY:

4798

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.150

AC:

6234

AN:

41524

American (AMR)

AF:

0.0476

AC:

729

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0374

AC:

130

AN:

3472

East Asian (EAS)

AF:

0.208

AC:

1075

AN:

5180

South Asian (SAS)

AF:

0.0607

AC:

293

AN:

4830

European-Finnish (FIN)

AF:

0.0466

AC:

494

AN:

10612

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00512

AC:

348

AN:

68016

Other (OTH)

AF:

0.0558

AC:

118

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

425

850

1276

1701

2126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0166

Hom.:

Bravo

AF:

0.0676

Asia WGS

AF:

0.159

AC:

551

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(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