Genetic Variant ESRP1:p.Asp157Asp (chr8-94646263-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_017697.4(ESRP1):c.471C>T(p.Asp157Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,607,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ESRP1
NM_017697.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

1 publications found

Variant links:

Genes affected

ESRP1 (HGNC:25966): (epithelial splicing regulatory protein 1) ESPR1 is an epithelial cell-type-specific splicing regulator (Warzecha et al., 2009 [PubMed 19285943]).[supplied by OMIM, Aug 2009]

ESRP1 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
hearing loss, autosomal recessive 109
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ESRP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.123).

BP7

Synonymous conserved (PhyloP=0.308 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017697.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRP1	NM_017697.4	MANE Select	c.471C>T	p.Asp157Asp	synonymous	Exon 4 of 16	NP_060167.2	Q6NXG1-1
ESRP1	NM_001034915.3		c.471C>T	p.Asp157Asp	synonymous	Exon 4 of 16	NP_001030087.2	Q6NXG1-3
ESRP1	NM_001122826.2		c.471C>T	p.Asp157Asp	synonymous	Exon 4 of 15	NP_001116298.1	Q6NXG1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRP1	ENST00000433389.8	TSL:1 MANE Select	c.471C>T	p.Asp157Asp	synonymous	Exon 4 of 16	ENSP00000405738.2	Q6NXG1-1
ESRP1	ENST00000358397.9	TSL:1	c.471C>T	p.Asp157Asp	synonymous	Exon 4 of 16	ENSP00000351168.5	Q6NXG1-3
ESRP1	ENST00000423620.6	TSL:1	c.471C>T	p.Asp157Asp	synonymous	Exon 4 of 15	ENSP00000407349.2	Q6NXG1-5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000728

AC:

AN:

247130

AF XY:

0.0000746

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1455616

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

724442

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33274

American (AMR)

AF:

0.00

AC:

AN:

44418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39556

South Asian (SAS)

AF:

0.000397

AC:

AN:

85704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1107394

Other (OTH)

AF:

0.00

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

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:

0.0000460

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41542

American (AMR)

AF:

0.000196

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

2.4

(source)

DANN

Benign

0.34

PhyloP100

0.31

PromoterAI

-0.024

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over