7-98304254-G-A

Position:

• chr7-98304254-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018842.5(BAIAP2L1):​c.1364C>T​(p.Ser455Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: BAIAP2L1 NM_018842.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0310

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06357944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAIAP2L1	NM_018842.5	c.1364C>T	p.Ser455Leu	missense_variant	12/14	ENST00000005260.9	NP_061330.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAIAP2L1	ENST00000005260.9	c.1364C>T	p.Ser455Leu	missense_variant	12/14	1	NM_018842.5	ENSP00000005260.8
BAIAP2L1	ENST00000480580.1	n.631C>T		non_coding_transcript_exon_variant	2/2	4
BRI3	ENST00000491463.4	n.72-2229G>A		intron_variant		4		ENSP00000459133.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461164 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726874

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000596

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 24, 2024

The c.1364C>T (p.S455L) alteration is located in exon 12 (coding exon 12) of the BAIAP2L1 gene. This alteration results from a C to T substitution at nucleotide position 1364, causing the serine (S) at amino acid position 455 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	Benign	0.070
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.35
DANN	Benign	0.93
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.036
Sift	Benign	0.29	T
Sift4G	Benign	0.29	T
Polyphen		0.010	B
Vest4		0.18
MutPred		0.29		Loss of phosphorylation at S455 (P = 0.0063);
MVP		0.092
MPC		0.18
ClinPred		0.095	T
GERP RS		-4.7
Varity_R		0.024
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs896193988; hg19: chr7-97933566;