14-96264343-T-A

Position:

• chr14-96264343-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000710.4(BDKRB1):​c.661T>A​(p.Phe221Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)
• Consequence: BDKRB1 NM_000710.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73

Genes affected

BDKRB1 (HGNC:1029): (bradykinin receptor B1) Bradykinin, a 9 aa peptide, is generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The protein encoded by this gene belongs to the G-protein coupled receptor 1 family. Two types of G-protein coupled receptors have been found which bind bradykinin and mediate responses to these pathophysiologic conditions. The protein encoded by this gene is one of these receptors and is synthesized de novo following tissue injury. Receptor binding leads to an increase in the cytosolic calcium ion concentration, ultimately resulting in chronic and acute inflammatory responses. [provided by RefSeq, Aug 2020]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2411567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB1	NM_000710.4	c.661T>A	p.Phe221Ile	missense_variant	3/3	ENST00000216629.11	NP_000701.2
LOC124903375	XR_007064322.1	n.212+4026A>T		intron_variant, non_coding_transcript_variant
BDKRB1	NM_001386007.1	c.661T>A	p.Phe221Ile	missense_variant	2/2		NP_001372936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB1	ENST00000216629.11	c.661T>A	p.Phe221Ile	missense_variant	3/3	1	NM_000710.4	ENSP00000216629	P1
BDKRB1	ENST00000553356.1	c.661T>A	p.Phe221Ile	missense_variant	3/5	1		ENSP00000452064
	ENST00000553638.1	n.256+4026A>T		intron_variant, non_coding_transcript_variant		2
BDKRB1	ENST00000611804.1	c.661T>A	p.Phe221Ile	missense_variant	1/1			ENSP00000479276	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

The c.661T>A (p.F221I) alteration is located in exon 3 (coding exon 1) of the BDKRB1 gene. This alteration results from a T to A substitution at nucleotide position 661, causing the phenylalanine (F) at amino acid position 221 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	T;.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	2.9	M;.;M
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.30	N;N;.
REVEL	Benign	0.13
Sift	Benign	0.12	T;T;.
Sift4G	Benign	0.50	T;T;T
Polyphen		0.59	P;B;P
Vest4		0.41
MutPred		0.60		Loss of catalytic residue at F221 (P = 0.0584);Loss of catalytic residue at F221 (P = 0.0584);Loss of catalytic residue at F221 (P = 0.0584);
MVP		0.39
MPC		0.40
ClinPred		0.86	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-96730680;