3-186617180-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001622.4(AHSG):c.410-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000541 in 1,605,738 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (5 hom.)
• Consequence: AHSG NM_001622.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002577
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425

Genes affected

AHSG (HGNC:349): (alpha 2-HS glycoprotein) The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-186617180-C-T is Benign according to our data. Variant chr3-186617180-C-T is described in ClinVar as [Benign]. Clinvar id is 737830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHSG	NM_001622.4	c.410-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000411641.7
AHSG	NM_001354571.2	c.410-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AHSG	NM_001354572.2	c.407-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AHSG	NM_001354573.2	c.410-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHSG	ENST00000411641.7	c.410-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001622.4	P3
HRG-AS1	ENST00000630178.2	n.239-37214G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152198 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00119 AC: 293 AN: 245668 Hom.: 3 AF XY: 0.00109 AC XY: 144 AN XY: 132570

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0127

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.000483 AC: 702 AN: 1453422 Hom.: 5 Cov.: 32 AF XY: 0.000446 AC XY: 322 AN XY: 722180

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0121

Gnomad4 NFE exome AF: 0.0000280

Gnomad4 OTH exome AF: 0.000417

GnomAD4 genome AF: 0.00110 AC: 167 AN: 152316 Hom.: 2 Cov.: 32 AF XY: 0.00172 AC XY: 128 AN XY: 74476

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000312 Hom.: 0

Bravo AF: 0.0000567

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.2
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
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: rs181773787; hg19: chr3-186334969;