11-64989278-G-C

Variant names:

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

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>G​(p.Pro226Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,600,906 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000097 (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=0.02767086).

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>G	p.Pro226Ala	missense	Exon 3 of 3	NP_612465.3
	BATF2	NM_001300807.2		c.604C>G	p.Pro202Ala	missense	Exon 2 of 2	NP_001287736.1	B4DV37
	BATF2	NM_001300808.2		c.421C>G	p.Pro141Ala	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>G	p.Pro226Ala	missense	Exon 3 of 3	ENSP00000301887.4	Q8N1L9-1
	BATF2	ENST00000435842.2	TSL:1	c.421C>G	p.Pro141Ala	missense	Exon 2 of 2	ENSP00000398911.2	Q8N1L9-2
	BATF2	ENST00000527716.1	TSL:2	c.604C>G	p.Pro202Ala	missense	Exon 2 of 2	ENSP00000434915.1	B4DV37

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000375 AC: 9 AN: 240006 AF XY: 0.0000309

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000152

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: 0.000518

GnomAD4 exome AF: 0.00000966 AC: 14 AN: 1448716 Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9 AN XY: 719610

African (AFR) AF: 0.00 AC: 0 AN: 33164

American (AMR) AF: 0.000162 AC: 7 AN: 43210

Ashkenazi Jewish (ASJ) AF: 0.0000399 AC: 1 AN: 25038

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39568

South Asian (SAS) AF: 0.0000236 AC: 2 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: 0.00000181 AC: 2 AN: 1104678

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

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41452

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000213 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000824 AC: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.91
DANN	Benign	0.49
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.028	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	0.024
Sift	Benign	0.23	T
Sift4G	Benign	0.55	T
Polyphen		0.0030	B
Vest4		0.057
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.31
MPC		0.047
ClinPred		0.029	T
GERP RS		-1.2
Varity_R		0.022
gMVP		0.14
Mutation Taster		=100/0	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;