Genetic Variant NM_004332.4:c.75C>T (chr6-3118815-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_004332.4(BPHL):c.75C>T(p.His25His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,244,122 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

BPHL
NM_004332.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.676

Publications

0 publications found

Variant links:

Genes affected

BPHL (HGNC:1094): (biphenyl hydrolase like) This gene encodes a member of the serine protease family of hydrolytic enzymes which contain a serine in their active site. The encoded protein may play a role in activation of the antiviral prodrug valacyclovir. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jan 2009]

BPHL links:

LOC107986556 (HGNC:):

LOC107986556 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=-0.676 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004332.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BPHL	NM_004332.4	MANE Select	c.75C>T	p.His25His	synonymous	Exon 1 of 7	NP_004323.2	Q86WA6-1
BPHL	NM_001302777.1		c.-205C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001289706.1	Q49AI2
BPHL	NM_001302777.1		c.-205C>T		5_prime_UTR	Exon 1 of 8	NP_001289706.1	Q49AI2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BPHL	ENST00000380379.10	TSL:1 MANE Select	c.75C>T	p.His25His	synonymous	Exon 1 of 7	ENSP00000369739.5	Q86WA6-1
BPHL	ENST00000424847.6	TSL:1	n.75C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000394072.2	F2Z2Q1
BPHL	ENST00000430655.6	TSL:1	n.75C>T		non_coding_transcript_exon	Exon 1 of 9	ENSP00000396637.2	F2Z2Q1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1091902

Hom.:

Cov.:

AF XY:

0.00000968

AC XY:

AN XY:

516490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23012

American (AMR)

AF:

0.00

AC:

AN:

8428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14432

East Asian (EAS)

AF:

0.00

AC:

AN:

26562

South Asian (SAS)

AF:

0.00

AC:

AN:

21404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4204

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

923306

Other (OTH)

AF:

0.00

AC:

AN:

44058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

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:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.5

(source)

DANN

Benign

0.89

PhyloP100

-0.68

PromoterAI

0.0045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over