NM_007049.5:c.400G>C

Variant names:

• chr6-26459798-G-C
• rs373825818
• NM_007049.5:c.400G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007049.5(BTN2A1):​c.400G>C​(p.Asp134His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTN2A1 NM_007049.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

Genes affected

BTN2A1 (HGNC:1136): (butyrophilin subfamily 2 member A1) This gene encodes a member of the immunoglobulin superfamily. The gene is located in a cluster of butyrophilin-like genes in the juxta-telomeric region of the major histocompatibility complex on chromosome 6. A pseudogene of this gene has been identified in this cluster. The encoded protein is an integral plasma membrane protein involved in lipid, fatty-acid, and sterol metabolism. Alterations in this gene may be associated with several disease states including metabolic syndrome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

ENSG00000291336 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15178731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A1	NM_007049.5	c.400G>C	p.Asp134His	missense_variant	Exon 3 of 8	ENST00000312541.10	NP_008980.1
BTN2A1	NM_001197233.3	c.217G>C	p.Asp73His	missense_variant	Exon 2 of 7		NP_001184162.1
BTN2A1	NM_078476.4	c.400G>C	p.Asp134His	missense_variant	Exon 3 of 8		NP_510961.1
BTN2A1	NM_001197234.3	c.400G>C	p.Asp134His	missense_variant	Exon 3 of 8		NP_001184163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10	c.400G>C	p.Asp134His	missense_variant	Exon 3 of 8	1	NM_007049.5	ENSP00000312158.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251124 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135728

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000137 AC: 2 AN: 1461768 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727180

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	.;T;.;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	.;L;.;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D
REVEL	Benign	0.041
Sift	Benign	0.047	D;D;D;T;D
Sift4G	Uncertain	0.039	D;D;T;T;T
Polyphen		0.36	.;B;.;.;.
Vest4		0.31
MutPred		0.46		.;Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.24
MPC		0.15
ClinPred		0.43	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.30

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: rs373825818; hg19: chr6-26460026;