7-107580838-C-G

Position:

• chr7-107580838-C-G

Variant summary

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

The NM_018844.4(BCAP29):​c.66C>G​(p.Phe22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,437,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BCAP29 NM_018844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.703

Genes affected

BCAP29 (HGNC:24131): (B cell receptor associated protein 29) Involved in osteoblast differentiation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DUS4L-BCAP29 (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=0.09061813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAP29	NM_018844.4	c.66C>G	p.Phe22Leu	missense_variant	2/8	ENST00000005259.9
DUS4L-BCAP29	NR_163940.2	n.1055C>G		non_coding_transcript_exon_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAP29	ENST00000005259.9	c.66C>G	p.Phe22Leu	missense_variant	2/8	1	NM_018844.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1437356 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 714680

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

Alfa AF: 0.000223 Hom.: 0

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

Jun 21, 2021

The c.66C>G (p.F22L) alteration is located in exon 1 (coding exon 1) of the BCAP29 gene. This alteration results from a C to G substitution at nucleotide position 66, causing the phenylalanine (F) at amino acid position 22 to be replaced by a leucine (L). 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	Uncertain	0.52
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.79
DEOGEN2	Benign	0.042	T;.;T;.;T;T;T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.091	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N;.;.;.;N;.;N
MutationTaster	Benign	0.96	D;D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.6	N;N;N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0010	B;.;.;.;B;B;.;.
Vest4		0.30
MutPred		0.52		Gain of catalytic residue at F22 (P = 0.079);Gain of catalytic residue at F22 (P = 0.079);Gain of catalytic residue at F22 (P = 0.079);Gain of catalytic residue at F22 (P = 0.079);Gain of catalytic residue at F22 (P = 0.079);Gain of catalytic residue at F22 (P = 0.079);Gain of catalytic residue at F22 (P = 0.079);Gain of catalytic residue at F22 (P = 0.079);
MVP		0.20
MPC		0.040
ClinPred		0.20	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1303562851; hg19: chr7-107221283;