chr1-117442154-A-T

Variant names:

• chr1-117442154-A-T
• rs2306444
• NM_006699.5:c.856-77A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006699.5(MAN1A2):​c.856-77A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 913,300 control chromosomes in the GnomAD database, including 41,600 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5741 hom., cov: 32)
  • Exomes 𝑓: 0.30 (35859 hom.)
• Consequence: MAN1A2 NM_006699.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 5 publications found

Genes affected

MAN1A2 (HGNC:6822): (mannosidase alpha class 1A member 2) Alpha-mannosidases function at different stages of N-glycan maturation in mammalian cells. See MAN2A1 (MIM 154582) for general information.[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1A2	NM_006699.5	c.856-77A>T		intron_variant	Intron 5 of 12	ENST00000356554.7	NP_006690.1
MAN1A2	XM_006710302.4	c.856-77A>T		intron_variant	Intron 5 of 13		XP_006710365.1
MAN1A2	XM_011540536.4	c.856-77A>T		intron_variant	Intron 5 of 12		XP_011538838.1
MAN1A2	XM_017000115.2	c.856-77A>T		intron_variant	Intron 5 of 6		XP_016855604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1A2	ENST00000356554.7	c.856-77A>T		intron_variant	Intron 5 of 12	1	NM_006699.5	ENSP00000348959.3
MAN1A2	ENST00000449370.6	c.52-77A>T		intron_variant	Intron 1 of 8	2		ENSP00000412706.2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39222 AN: 151916 Hom.: 5735 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.298 AC: 226936 AN: 761266 Hom.: 35859 AF XY: 0.299 AC XY: 121023 AN XY: 404458

African (AFR) AF: 0.145 AC: 2883 AN: 19852

American (AMR) AF: 0.186 AC: 7860 AN: 42364

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 2746 AN: 20912

East Asian (EAS) AF: 0.464 AC: 16645 AN: 35908

South Asian (SAS) AF: 0.314 AC: 21748 AN: 69166

European-Finnish (FIN) AF: 0.354 AC: 17659 AN: 49886

Middle Eastern (MID) AF: 0.147 AC: 604 AN: 4106

European-Non Finnish (NFE) AF: 0.304 AC: 146379 AN: 482084

Other (OTH) AF: 0.281 AC: 10412 AN: 36988

GnomAD4 genome AF: 0.258 AC: 39244 AN: 152034 Hom.: 5741 Cov.: 32 AF XY: 0.261 AC XY: 19375 AN XY: 74338

African (AFR) AF: 0.150 AC: 6217 AN: 41482

American (AMR) AF: 0.214 AC: 3273 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2459 AN: 5168

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4818

European-Finnish (FIN) AF: 0.364 AC: 3850 AN: 10568

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20600 AN: 67948

Other (OTH) AF: 0.249 AC: 526 AN: 2110

Alfa AF: 0.186 Hom.: 456

Bravo AF: 0.241

Asia WGS AF: 0.408 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs2306444; hg19: chr1-117984776; COSMIC: COSV62976990;