6-26501302-A-G

Variant names:

• chr6-26501302-A-G
• NM_001732.3:c.16A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001732.3(BTN1A1):​c.16A>G​(p.Ser6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTN1A1 NM_001732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.470

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06525445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN1A1	NM_001732.3	c.16A>G	p.Ser6Gly	missense_variant	Exon 2 of 8	ENST00000684113.1	NP_001723.2
LOC107986583	XR_001744057.3	n.5891-13158T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN1A1	ENST00000684113.1	c.16A>G	p.Ser6Gly	missense_variant	Exon 2 of 8		NM_001732.3	ENSP00000507193.1
BTN1A1	ENST00000244513.10	c.16A>G	p.Ser6Gly	missense_variant	Exon 1 of 7	1		ENSP00000244513.6
ENSG00000291336	ENST00000707189.1	n.1000-51885A>G		intron_variant	Intron 1 of 1
ENSG00000291338	ENST00000707191.1	n.1001-31403A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16A>G (p.S6G) alteration is located in exon 1 (coding exon 1) of the BTN1A1 gene. This alteration results from a A to G substitution at nucleotide position 16, causing the serine (S) at amino acid position 6 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.1
DANN	Benign	0.81
DEOGEN2	Benign	0.093	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.36	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.83	N;.
REVEL	Benign	0.011
Sift	Benign	0.57	T;.
Sift4G	Benign	0.38	T;T
Polyphen		0.0	B;.
Vest4		0.20
MutPred		0.33		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.25
MPC		0.41
ClinPred		0.030	T
GERP RS		1.6
Varity_R		0.061
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-26501530;