chr6-3137488-C-G

Variant names:

• chr6-3137488-C-G
• rs1762045441
• NM_004332.4:c.659C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004332.4(BPHL):​c.659C>G​(p.Pro220Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BPHL NM_004332.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.94
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22237557).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPHL	NM_004332.4	MANE Select	c.659C>G	p.Pro220Arg	missense	Exon 5 of 7	NP_004323.2	Q86WA6-1
	BPHL	NM_001302777.1		c.608C>G	p.Pro203Arg	missense	Exon 6 of 8	NP_001289706.1	Q49AI2
	BPHL	NR_026648.2		n.1186+66C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPHL	ENST00000380379.10	TSL:1 MANE Select	c.659C>G	p.Pro220Arg	missense	Exon 5 of 7	ENSP00000369739.5	Q86WA6-1
	BPHL	ENST00000380375.4	TSL:1	c.608C>G	p.Pro203Arg	missense	Exon 5 of 7	ENSP00000369734.3	Q86WA6-2
	BPHL	ENST00000424847.6	TSL:1	n.*752C>G		non_coding_transcript_exon	Exon 6 of 8	ENSP00000394072.2	F2Z2Q1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.14
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.021
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.20	N
REVEL	Uncertain	0.33
Sift	Benign	0.93	T
Sift4G	Benign	0.78	T
Polyphen		0.0050	B
Vest4		0.46
MutPred		0.61		Gain of MoRF binding (P = 0.0106)
MVP		0.64
MPC		0.21
ClinPred		0.72	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.80
Mutation Taster		=35/65	disease causing

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: rs1762045441; hg19: chr6-3137722;