11-64989278-G-T

Variant names:

• chr11-64989278-G-T
• rs151056191
• NM_138456.4:c.676C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138456.4(BATF2):​c.676C>A​(p.Pro226Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P226S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BATF2 NM_138456.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 0 publications found

Genes affected

BATF2 (HGNC:25163): (basic leucine zipper ATF-like transcription factor 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in defense response to protozoan; myeloid dendritic cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05574149).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138456.4. 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
	BATF2	NM_138456.4	MANE Select	c.676C>A	p.Pro226Thr	missense	Exon 3 of 3	NP_612465.3
	BATF2	NM_001300807.2		c.604C>A	p.Pro202Thr	missense	Exon 2 of 2	NP_001287736.1	B4DV37
	BATF2	NM_001300808.2		c.421C>A	p.Pro141Thr	missense	Exon 2 of 2	NP_001287737.1	Q8N1L9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BATF2	ENST00000301887.9	TSL:1 MANE Select	c.676C>A	p.Pro226Thr	missense	Exon 3 of 3	ENSP00000301887.4	Q8N1L9-1
	BATF2	ENST00000435842.2	TSL:1	c.421C>A	p.Pro141Thr	missense	Exon 2 of 2	ENSP00000398911.2	Q8N1L9-2
	BATF2	ENST00000527716.1	TSL:2	c.604C>A	p.Pro202Thr	missense	Exon 2 of 2	ENSP00000434915.1	B4DV37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 240006 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 6.90e-7 AC: 1 AN: 1448716 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719610

⚠️ 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: 33164

American (AMR) AF: 0.0000231 AC: 1 AN: 43210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.00 AC: 0 AN: 84708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104678

Other (OTH) AF: 0.00 AC: 0 AN: 59756

⚠️ 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 Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.6
DANN	Benign	0.82
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.18
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.029
Sift	Benign	0.075	T
Sift4G	Benign	0.24	T
Polyphen		0.019	B
Vest4		0.042
MutPred		0.18		Gain of phosphorylation at P226 (P = 0.0211)
MVP		0.33
MPC		0.057
ClinPred		0.035	T
GERP RS		-1.2
Varity_R		0.035
gMVP		0.24
Mutation Taster		=99/1	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: rs151056191; hg19: chr11-64756750;