chr7-98294092-G-A

Position:

• chr7-98294092-G-A

Variant summary

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

The NM_018842.5(BAIAP2L1):​c.1442C>T​(p.Ala481Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BAIAP2L1 NM_018842.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

Genes affected

BAIAP2L1 (HGNC:21649): (BAR/IMD domain containing adaptor protein 2 like 1) This gene encodes a member of the IMD (IRSp53/MIM homology domain) family. Members of this family can be subdivided in two groups, the IRSp53-like and MIM-like, based on the presence or absence of the SH3 (Src homology 3) domain. The protein encoded by this gene contains a conserved IMD, also known as F-actin bundling domain, at the N-terminus, and a canonical SH3 domain near the C-terminus, so it belongs to the IRSp53-like group. This protein is the substrate for insulin receptor tyrosine kinase and binds to the small GTPase Rac. It is involved in signal transduction pathways that link deformation of the plasma membrane and remodeling of the actin cytoskeleton. It also promotes actin assembly and membrane protrusions when overexpressed in mammalian cells, and is essential to the formation of a potent actin assembly complex during EHEC (Enterohemorrhagic Escherichia coli) pedestal formation. [provided by RefSeq, Oct 2009]

BRI3 (HGNC:1109): (brain protein I3) Enables identical protein binding activity. Predicted to be located in azurophil granule membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09941155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAIAP2L1	NM_018842.5	c.1442C>T	p.Ala481Val	missense_variant	13/14	ENST00000005260.9	NP_061330.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAIAP2L1	ENST00000005260.9	c.1442C>T	p.Ala481Val	missense_variant	13/14	1	NM_018842.5	ENSP00000005260.8
BRI3	ENST00000491463.4	n.71+11639G>A		intron_variant		4		ENSP00000459133.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jun 30, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.068
Sift	Benign	0.16	T
Sift4G	Benign	0.41	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.18		Gain of methylation at K482 (P = 0.039);
MVP		0.46
MPC		0.20
ClinPred		0.24	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800082754; hg19: chr7-97923404;