6-26501737-T-C

Variant names:

• chr6-26501737-T-C
• rs768070610
• NM_001732.3:c.227T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001732.3(BTN1A1):​c.227T>C​(p.Val76Ala) 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 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. V76G) 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: 0.573
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29069757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN1A1	NM_001732.3	c.227T>C	p.Val76Ala	missense_variant	Exon 3 of 8	ENST00000684113.1	NP_001723.2
LOC107986583	XR_001744057.3	n.5891-13593A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN1A1	ENST00000684113.1	c.227T>C	p.Val76Ala	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: 1461508 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727102

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		0.57
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Benign	0.24
Sift	Uncertain	0.029	D;.
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.96	D;.
Vest4		0.10
MutPred		0.64		Gain of disorder (P = 0.0378);Gain of disorder (P = 0.0378);
MVP		0.69
MPC		0.70
ClinPred		0.72	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.51
Mutation Taster		=90/10	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: rs768070610; hg19: chr6-26501965;