7-98315625-A-ATAATAATAAT

Variant names:

• chr7-98315625-A-ATAATAATAAT
• rs372695844
• NM_018842.5:c.487-14_487-13insATTATTATTA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_018842.5(BAIAP2L1):​c.487-14_487-13insATTATTATTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 149,110 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: BAIAP2L1 NM_018842.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 7-98315625-A-ATAATAATAAT is Benign according to our data. Variant chr7-98315625-A-ATAATAATAAT is described in ClinVar as Likely_benign. ClinVar VariationId is 2776134.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018842.5. 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
	BAIAP2L1	NM_018842.5	MANE Select	c.487-14_487-13insATTATTATTA		intron	N/A	NP_061330.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAIAP2L1	ENST00000005260.9	TSL:1 MANE Select	c.487-14_487-13insATTATTATTA		intron	N/A	ENSP00000005260.8	Q9UHR4
	BAIAP2L1	ENST00000462558.5	TSL:1	n.703-14_703-13insATTATTATTA		intron	N/A
	BAIAP2L1	ENST00000869917.1		c.502-14_502-13insATTATTATTA		intron	N/A	ENSP00000539976.1

Frequencies

GnomAD3 genomes AF: 0.000235 AC: 35 AN: 149110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000400

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000232 AC: 228 AN: 982008 Hom.: 5 Cov.: 14 AF XY: 0.000218 AC XY: 105 AN XY: 481162

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19944

American (AMR) AF: 0.000127 AC: 2 AN: 15790

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 7 AN: 15264

East Asian (EAS) AF: 0.00 AC: 0 AN: 26770

South Asian (SAS) AF: 0.000188 AC: 6 AN: 31972

European-Finnish (FIN) AF: 0.0000282 AC: 1 AN: 35420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2930

European-Non Finnish (NFE) AF: 0.000253 AC: 201 AN: 794236

Other (OTH) AF: 0.000277 AC: 11 AN: 39682

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000235 AC: 35 AN: 149110 Hom.: 0 Cov.: 32 AF XY: 0.000275 AC XY: 20 AN XY: 72788

African (AFR) AF: 0.00 AC: 0 AN: 40422

American (AMR) AF: 0.000400 AC: 6 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 5 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.000341 AC: 23 AN: 67470

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.0000614 Hom.: 293

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs372695844;

hg19: chr7-97944937;