rs775717650

Variant names:

• chr8-103213038-A-G
• rs775717650
• NM_024812.3:c.280A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024812.3(BAALC):​c.280A>G​(p.Ser94Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: BAALC NM_024812.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.361
• Publications: 0 publications found

Genes affected

BAALC (HGNC:14333): (BAALC binder of MAP3K1 and KLF4) This gene was identified by gene expression studies in patients with acute myeloid leukemia (AML). The gene is conserved among mammals and is not found in lower organisms. Tissues that express this gene develop from the neuroectoderm. Multiple alternatively spliced transcript variants that encode different proteins have been described for this gene; however, some of the transcript variants are found only in AML cell lines. [provided by RefSeq, Jul 2008]

BAALC-AS1 (HGNC:50461): (BAALC antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026372373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024812.3. 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
	BAALC	NM_024812.3	MANE Select	c.280A>G	p.Ser94Gly	missense	Exon 2 of 3	NP_079088.1	Q8WXS3-2
	BAALC	NM_001364874.1		c.385A>G	p.Ser129Gly	missense	Exon 3 of 4	NP_001351803.1	Q8WXS3-1
	BAALC	NM_001024372.2		c.161-14951A>G		intron	N/A	NP_001019543.1	Q8WXS3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAALC	ENST00000309982.10	TSL:1 MANE Select	c.280A>G	p.Ser94Gly	missense	Exon 2 of 3	ENSP00000312457.5	Q8WXS3-2
	BAALC	ENST00000438105.2	TSL:1	c.161-14951A>G		intron	N/A	ENSP00000395024.2	Q8WXS3-6
	BAALC	ENST00000297574.6	TSL:3	c.385A>G	p.Ser129Gly	missense	Exon 3 of 4	ENSP00000297574.6	Q8WXS3-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251192 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461824 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74378

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

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.36
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.088
Sift	Benign	0.28	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.091		Loss of phosphorylation at S129 (P = 0.0585)
MVP		0.20
MPC		0.10
ClinPred		0.028	T
GERP RS		-1.5
Varity_R		0.035
gMVP		0.12
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs775717650; hg19: chr8-104225266;