6-26501679-A-G

Variant names:

• chr6-26501679-A-G
• rs1763801493
• NM_001732.3:c.169A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001732.3(BTN1A1):​c.169A>G​(p.Ser57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,714 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S57C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTN1A1 NM_001732.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

BTN1A1 (HGNC:1135): (butyrophilin subfamily 1 member A1) Butyrophilin is the major protein associated with fat droplets in the milk. It is a member of the immunoglobulin superfamily. It may have a cell surface receptor function. The human butyrophilin gene is localized in the major histocompatibility complex (MHC) class I region of 6p and may have arisen relatively recently in evolution by the shuffling of exons between 2 ancestral gene families [provided by RefSeq, Jul 2008]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN1A1	NM_001732.3	c.169A>G	p.Ser57Gly	missense_variant	Exon 3 of 8	ENST00000684113.1	NP_001723.2
LOC107986583	XR_001744057.3	n.5891-13535T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN1A1	ENST00000684113.1	c.169A>G	p.Ser57Gly	missense_variant	Exon 3 of 8		NM_001732.3	ENSP00000507193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461714 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727174

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111978

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.4	M;.
PhyloP100		2.2
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.29
Sift	Uncertain	0.017	D;.
Sift4G	Uncertain	0.037	D;D
Polyphen		0.99	D;.
Vest4		0.41
MutPred		0.42		Loss of stability (P = 0.0786);Loss of stability (P = 0.0786);
MVP		0.82
MPC		1.2
ClinPred		0.97	D
GERP RS		4.7
PromoterAI		-0.018	Neutral
Varity_R		0.20
gMVP		0.62
Mutation Taster		=87/13	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: rs1763801493; hg19: chr6-26501907;